Glial cells expressing neuron-glial antigen 2 (NG2), also known as oligodendrocyte progenitor cells (OPCs), play a critical role in maintaining brain health. However, their ability to differentiate after ischemic injury is poorly understood. The aim of this study was to investigate the properties and functions of NG2 glia in the ischemic brain. Using transgenic mice, we selectively labeled NG2-expressing cells and their progeny in both healthy brain and after focal cerebral ischemia (FCI). Using single-cell RNA sequencing, we classified the labeled glial cells into five distinct subpopulations based on their gene expression patterns. Additionally, we examined the membrane properties of these cells using the patch-clamp technique. Of the identified subpopulations, three were identified as OPCs, whereas the fourth subpopulation had characteristics indicative of cells likely to develop into oligodendrocytes. The fifth subpopulation of NG2 glia showed astrocytic markers and had similarities to neural progenitor cells. Interestingly, this subpopulation was present in both healthy and post-ischemic tissue; however, its gene expression profile changed after ischemia, with increased numbers of genes related to neurogenesis. Immunohistochemical analysis confirmed the temporal expression of neurogenic genes and showed an increased presence of NG2 cells positive for Purkinje cell protein-4 at the periphery of the ischemic lesion 12 days after FCI, as well as NeuN-positive NG2 cells 28 and 60 days after injury. These results suggest the potential development of neuron-like cells arising from NG2 glia in the ischemic tissue. Our study provides insights into the plasticity of NG2 glia and their capacity for neurogenesis after stroke.

2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Cellular Neurophysiology Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Cell and Developmental Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Genomics and Bioinformatics Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

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Adams, K. L., & Gallo, V. (2018). The diversity and disparity of the glial scar. Nature Neuroscience, 21(1), 9-15. https://doi.org/10.1038/s41593-017-0033-9

Akay, L. A., Effenberger, A. H., & Tsai, L. H. (2021). Cell of all trades: Oligodendrocyte precursor cells in synaptic, vascular, and immune function. Genes & Development, 35(3-4), 180-198. https://doi.org/10.1101/gad.344218.120

Anderova, M., Antonova, T., Petrik, D., Neprasova, H., Chvatal, A., & Sykova, E. (2004). Voltage-dependent potassium currents in hypertrophied rat astrocytes after a cortical stab wound. Glia, 48(4), 311-326. https://doi.org/10.1002/glia.20076

Andersen, J., Urban, N., Achimastou, A., Ito, A., Simic, M., Ullom, K., Martynoga, B., Lebel, M., Goritz, C., Frisen, J., Nakafuku, M., & Guillemot, F. (2014). A transcriptional mechanism integrating inputs from extracellular signals to activate hippocampal stem cells. Neuron, 83(5), 1085-1097. https://doi.org/10.1016/j.neuron.2014.08.004

Androvic, P., Kirdajova, D., Tureckova, J., Zucha, D., Rohlova, E., Abaffy, P., Kriska, J., Valny, M., Anderova, M., Kubista, M., & Valihrach, L. (2020). Decoding the transcriptional response to ischemic stroke in Young and aged mouse brain. Cell Reports, 31(11), 107777. https://doi.org/10.1016/j.celrep.2020.107777

Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., Harris, M. A., Hill, D. P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J. C., Richardson, J. E., Ringwald, M., Rubin, G. M., & Sherlock, G. (2000). Gene ontology: Tool for the unification of biology. The gene ontology consortium. Nature Genetics, 25(1), 25-29. https://doi.org/10.1038/75556

Bai, X., Zhao, N., Koupourtidou, C., Fang, L. P., Schwarz, V., Caudal, L. C., Zhao, R., Hirrlinger, J., Walz, W., Bian, S., Huang, W., Ninkovic, J., Kirchhoff, F., & Scheller, A. (2023). In the mouse cortex, oligodendrocytes regain a plastic capacity, transforming into astrocytes after acute injury. Developmental Cell, 58, 1153-1169.e5. https://doi.org/10.1016/j.devcel.2023.04.016

Becht, E., McInnes, L., Healy, J., Dutertre, C. A., Kwok, I. W. H., Ng, L. G., Ginhoux, F., & Newell, E. W. (2018). Dimensionality reduction for visualizing single-cell data using UMAP. Nature Biotechnology, 37, 38-44. https://doi.org/10.1038/nbt.4314

Beiter, R. M., Rivet-Noor, C., Merchak, A. R., Bai, R., Johanson, D. M., Slogar, E., Sol-Church, K., Overall, C. C., & Gaultier, A. (2022). Evidence for oligodendrocyte progenitor cell heterogeneity in the adult mouse brain. Scientific Reports, 12(1), 12921. https://doi.org/10.1038/s41598-022-17081-7

Bergles, D. E., Roberts, J. D., Somogyi, P., & Jahr, C. E. (2000). Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature, 405(6783), 187-191. https://doi.org/10.1038/35012083

Bergsland, M., Werme, M., Malewicz, M., Perlmann, T., & Muhr, J. (2006). The establishment of neuronal properties is controlled by Sox4 and Sox11. Genes & Development, 20(24), 3475-3486. https://doi.org/10.1101/gad.403406

Bernal, G. M., & Peterson, D. A. (2011). Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells. Aging Cell, 10(3), 466-482. https://doi.org/10.1111/j.1474-9726.2011.00694.x

Berninger, B., Costa, M. R., Koch, U., Schroeder, T., Sutor, B., Grothe, B., & Gotz, M. (2007). Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia. The Journal of Neuroscience, 27(32), 8654-8664. https://doi.org/10.1523/JNEUROSCI.1615-07.2007

Bernstein, S. L., Koo, J. H., Slater, B. J., Guo, Y., & Margolis, F. L. (2006). Analysis of optic nerve stroke by retinal Bex expression. Molecular Vision, 12(16), 147-155.

Biname, F. (2014). Transduction of extracellular cues into cell polarity: The role of the transmembrane proteoglycan NG2. Molecular Neurobiology, 50(2), 482-493. https://doi.org/10.1007/s12035-013-8610-8

Binder, J. X., Pletscher-Frankild, S., Tsafou, K., Stolte, C., O'Donoghue, S. I., Schneider, R., & Jensen, L. J. (2014). COMPARTMENTS: Unification and visualization of protein subcellular localization evidence. Database (Oxford), 2014, bau012. https://doi.org/10.1093/database/bau012

Boda, E., Vigano, F., Rosa, P., Fumagalli, M., Labat-Gest, V., Tempia, F., Abbracchio, M. P., Dimou, L., & Buffo, A. (2011). The GPR17 receptor in NG2 expressing cells: Focus on in vivo cell maturation and participation in acute trauma and chronic damage. Glia, 59(12), 1958-1973. https://doi.org/10.1002/glia.21237

Bonfanti, E., Gelosa, P., Fumagalli, M., Dimou, L., Vigano, F., Tremoli, E., Cimino, M., Sironi, L., & Abbracchio, M. P. (2017). The role of oligodendrocyte precursor cells expressing the GPR17 receptor in brain remodeling after stroke. Cell Death & Disease, 8(6), e2871. https://doi.org/10.1038/cddis.2017.256

Bordey, A., Lyons, S. A., Hablitz, J. J., & Sontheimer, H. (2001). Electrophysiological characteristics of reactive astrocytes in experimental cortical dysplasia. Journal of Neurophysiology, 85(4), 1719-1731. https://doi.org/10.1152/jn.2001.85.4.1719

Boulanger, J. J., & Messier, C. (2017a). Doublecortin in oligodendrocyte precursor cells in the adult mouse brain. Frontiers in Neuroscience, 11, 143. https://doi.org/10.3389/fnins.2017.00143

Boulanger, J. J., & Messier, C. (2017b). Unbiased stereological analysis of the fate of oligodendrocyte progenitor cells in the adult mouse brain and effect of reference memory training. Behavioural Brain Research, 329, 127-139. https://doi.org/10.1016/j.bbr.2017.04.027

Cai, W., Liu, H., Zhao, J., Chen, L. Y., Chen, J., Lu, Z., & Hu, X. (2017). Pericytes in brain injury and repair after ischemic stroke. Translational Stroke Research, 8(2), 107-121. https://doi.org/10.1007/s12975-016-0504-4

Casper, K. B., & McCarthy, K. D. (2006). GFAP-positive progenitor cells produce neurons and oligodendrocytes throughout the CNS. Molecular and Cellular Neurosciences, 31(4), 676-684. https://doi.org/10.1016/j.mcn.2005.12.006

Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., Clark, N. R., & Ma'ayan, A. (2013). Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics, 14, 128. https://doi.org/10.1186/1471-2105-14-128

Chen, Y., Fan, Z., & Wu, Q. (2021). Dexmedetomidine improves oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neurological injury through regulating SNHG11/miR-324-3p/VEGFA axis. Bioengineered, 12(1), 4794-4804. https://doi.org/10.1080/21655979.2021.1957071

Chittajallu, R., Aguirre, A., & Gallo, V. (2004). NG2-positive cells in the mouse white and grey matter display distinct physiological properties. The Journal of Physiology, 561(Pt 1), 109-122. https://doi.org/10.1113/jphysiol.2004.074252

Chvatal, A., Anderova, M., Ziak, D., & Sykova, E. (1999). Glial depolarization evokes a larger potassium accumulation around oligodendrocytes than around astrocytes in gray matter of rat spinal cord slices. Journal of Neuroscience Research, 56(5), 493-505. https://doi.org/10.1002/(SICI)1097-4547(19990601)56:5<493::AID-JNR5>3.0.CO;2-O

Clarke, L. E., Young, K. M., Hamilton, N. B., Li, H., Richardson, W. D., & Attwell, D. (2012). Properties and fate of oligodendrocyte progenitor cells in the corpus callosum, motor cortex, and piriform cortex of the mouse. The Journal of Neuroscience, 32(24), 8173-8185. https://doi.org/10.1523/JNEUROSCI.0928-12.2012

Cochard, L. M., Levros, L. C., Jr., Joppe, S. E., Pratesi, F., Aumont, A., & Fernandes, K. J. L. (2021). Manipulation of EGFR-induced signaling for the recruitment of quiescent neural stem cells in the adult mouse forebrain. Frontiers in Neuroscience, 15, 621076. https://doi.org/10.3389/fnins.2021.621076

Colak, G., Filiano, A. J., & Johnson, G. V. (2011). The application of permanent middle cerebral artery ligation in the mouse. Journal of Visualized Experiments, 53, 3039. https://doi.org/10.3791/3039

Da Silva, F., Zhang, K., Pinson, A., Fatti, E., Wilsch-Brauninger, M., Herbst, J., Vidal, V., Schedl, A., Huttner, W. B., & Niehrs, C. (2021). Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex. The EMBO Journal, 40(19), e108041. https://doi.org/10.15252/embj.2021108041

Dawson, M. R., Polito, A., Levine, J. M., & Reynolds, R. (2003). NG2-expressing glial progenitor cells: An abundant and widespread population of cycling cells in the adult rat CNS. Molecular and Cellular Neurosciences, 24(2), 476-488. https://doi.org/10.1016/s1044-7431(03)00210-0

Dayer, A. G., Cleaver, K. M., Abouantoun, T., & Cameron, H. A. (2005). New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. The Journal of Cell Biology, 168(3), 415-427. https://doi.org/10.1083/jcb.200407053

de Pablo, Y., Nilsson, M., Pekna, M., & Pekny, M. (2013). Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen-glucose deprivation and reperfusion. Histochemistry and Cell Biology, 140(1), 81-91. https://doi.org/10.1007/s00418-013-1110-0

Dean, T., Ghaemmaghami, J., Corso, J., & Gallo, V. (2023). The cortical NG2-glia response to traumatic brain injury. Glia, 71(5), 1164-1175. https://doi.org/10.1002/glia.24342

Delgado, A. C., Maldonado-Soto, A. R., Silva-Vargas, V., Mizrak, D., von Kanel, T., Tan, K. R., Paul, A., Madar, A., Cuervo, H., Kitajewski, J., Lin, C. S., & Doetsch, F. (2021). Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain. Science, 372(6547), 1205-1209. https://doi.org/10.1126/science.abg8467

Diers-Fenger, M., Kirchhoff, F., Kettenmann, H., Levine, J. M., & Trotter, J. (2001). AN2/NG2 protein-expressing glial progenitor cells in the murine CNS: Isolation, differentiation, and association with radial glia. Glia, 34(3), 213-228. https://doi.org/10.1002/glia.1055

Dimou, L., Simon, C., Kirchhoff, F., Takebayashi, H., & Gotz, M. (2008). Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. The Journal of Neuroscience, 28(41), 10434-10442. https://doi.org/10.1523/JNEUROSCI.2831-08.2008

Doetsch, F., Garcia-Verdugo, J. M., & Alvarez-Buylla, A. (1997). Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. The Journal of Neuroscience, 17(13), 5046-5061. https://doi.org/10.1523/JNEUROSCI.17-13-05046.1997

Enyedi, P., & Czirjak, G. (2010). Molecular background of leak K+ currents: Two-pore domain potassium channels. Physiological Reviews, 90(2), 559-605. https://doi.org/10.1152/physrev.00029.2009

Faiz, M., Sachewsky, N., Gascon, S., Bang, K. W., Morshead, C. M., & Nagy, A. (2015). Adult neural stem cells from the subventricular zone give rise to reactive astrocytes in the cortex after stroke. Cell Stem Cell, 17(5), 624-634. https://doi.org/10.1016/j.stem.2015.08.002

Feigenson, K., Reid, M., See, J., Crenshaw, E. B., 3rd, & Grinspan, J. B. (2009). Wnt signaling is sufficient to perturb oligodendrocyte maturation. Molecular and Cellular Neurosciences, 42(3), 255-265. https://doi.org/10.1016/j.mcn.2009.07.010

Fernandez, E. M., Diaz-Ceso, M. D., & Vilar, M. (2015). Brain expressed and X-linked (Bex) proteins are intrinsically disordered proteins (IDPs) and form new signaling hubs. PLoS One, 10(1), e0117206. https://doi.org/10.1371/journal.pone.0117206

Filippov, V., Kronenberg, G., Pivneva, T., Reuter, K., Steiner, B., Wang, L. P., Yamaguchi, M., Kettenmann, H., & Kempermann, G. (2003). Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Molecular and Cellular Neurosciences, 23(3), 373-382. https://doi.org/10.1016/s1044-7431(03)00060-5

Fruhbeis, C., Frohlich, D., Kuo, W. P., Amphornrat, J., Thilemann, S., Saab, A. S., Kirchhoff, F., Mobius, W., Goebbels, S., Nave, K. A., Schneider, A., Simons, M., Klugmann, M., Trotter, J., & Kramer-Albers, E. M. (2013). Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biology, 11(7), e1001604. https://doi.org/10.1371/journal.pbio.1001604

Fu, H., Cai, J., Clevers, H., Fast, E., Gray, S., Greenberg, R., Jain, M. K., Ma, Q., Qiu, M., Rowitch, D. H., Taylor, C. M., & Stiles, C. D. (2009). A genome-wide screen for spatially restricted expression patterns identifies transcription factors that regulate glial development. The Journal of Neuroscience, 29(36), 11399-11408. https://doi.org/10.1523/JNEUROSCI.0160-09.2009

Fumagalli, M., Daniele, S., Lecca, D., Lee, P. R., Parravicini, C., Fields, R. D., Rosa, P., Antonucci, F., Verderio, C., Trincavelli, M. L., Bramanti, P., Martini, C., & Abbracchio, M. P. (2011). Phenotypic changes, signaling pathway, and functional correlates of GPR17-expressing neural precursor cells during oligodendrocyte differentiation. The Journal of Biological Chemistry, 286(12), 10593-10604. https://doi.org/10.1074/jbc.M110.162867

Garcia, A. D., Doan, N. B., Imura, T., Bush, T. G., & Sofroniew, M. V. (2004). GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nature Neuroscience, 7(11), 1233-1241. https://doi.org/10.1038/nn1340

Ge, W. P., Yang, X. J., Zhang, Z., Wang, H. K., Shen, W., Deng, Q. D., & Duan, S. (2006). Long-term potentiation of neuron-glia synapses mediated by Ca2+−permeable AMPA receptors. Science, 312(5779), 1533-1537. https://doi.org/10.1126/science.1124669

Gene Ontology, Consortium. (2021). The gene ontology resource: Enriching a gold mine. Nucleic Acids Research, 49(D1), D325-D334. https://doi.org/10.1093/nar/gkaa1113

Grande, A., Sumiyoshi, K., Lopez-Juarez, A., Howard, J., Sakthivel, B., Aronow, B., Campbell, K., & Nakafuku, M. (2013). Environmental impact on direct neuronal reprogramming in vivo in the adult brain. Nature Communications, 4, 2373. https://doi.org/10.1038/ncomms3373

Guo, F., Maeda, Y., Ma, J., Xu, J., Horiuchi, M., Miers, L., Vaccarino, F., & Pleasure, D. (2010). Pyramidal neurons are generated from oligodendroglial progenitor cells in adult piriform cortex. The Journal of Neuroscience, 30(36), 12036-12049. https://doi.org/10.1523/JNEUROSCI.1360-10.2010

Guo, F., & Wang, Y. (2023). TCF7l2, a nuclear marker that labels premyelinating oligodendrocytes and promotes oligodendroglial lineage progression. Glia, 71(2), 143-154. https://doi.org/10.1002/glia.24249

Guo, Y., Liu, S., Zhang, X., Wang, L., Zhang, X., Hao, A., Han, A., & Yang, J. (2014). Sox11 promotes endogenous neurogenesis and locomotor recovery in mice spinal cord injury. Biochemical and Biophysical Research Communications, 446(4), 830-835. https://doi.org/10.1016/j.bbrc.2014.02.103

Gusel'nikova, V. V., & Korzhevskiy, D. E. (2015). NeuN As a neuronal nuclear antigen and neuron differentiation marker. Acta Naturae, 7(2), 42-47.

Hackett, A. R., Yahn, S. L., Lyapichev, K., Dajnoki, A., Lee, D. H., Rodriguez, M., Cammer, N., Pak, J., Mehta, S. T., Bodamer, O., Lemmon, V. P., & Lee, J. K. (2018). Injury type-dependent differentiation of NG2 glia into heterogeneous astrocytes. Experimental Neurology, 308, 72-79. https://doi.org/10.1016/j.expneurol.2018.07.001

Hamilton, T. G., Klinghoffer, R. A., Corrin, P. D., & Soriano, P. (2003). Evolutionary divergence of platelet-derived growth factor alpha receptor signaling mechanisms. Molecular and Cellular Biology, 23(11), 4013-4025. https://doi.org/10.1128/MCB.23.11.4013-4025.2003

Harashima, S., Wang, Y., Horiuchi, T., Seino, Y., & Inagaki, N. (2011). Purkinje cell protein 4 positively regulates neurite outgrowth and neurotransmitter release. Journal of Neuroscience Research, 89(10), 1519-1530. https://doi.org/10.1002/jnr.22688

Heinrich, C., Bergami, M., Gascon, S., Lepier, A., Vigano, F., Dimou, L., Sutor, B., Berninger, B., & Gotz, M. (2014). Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Reports, 3(6), 1000-1014. https://doi.org/10.1016/j.stemcr.2014.10.007

Hernandez, I. H., Villa-Gonzalez, M., Martin, G., Soto, M., & Perez-Alvarez, M. J. (2021). Glial cells as therapeutic approaches in brain ischemia-reperfusion injury. Cell, 10(7), 1639. https://doi.org/10.3390/cells10071639

Hesp, Z. C., Yoseph, R. Y., Suzuki, R., Jukkola, P., Wilson, C., Nishiyama, A., & McTigue, D. M. (2018). Proliferating NG2-cell-dependent angiogenesis and scar formation alter axon growth and functional recovery after spinal cord injury in mice. The Journal of Neuroscience, 38(6), 1366-1382. https://doi.org/10.1523/JNEUROSCI.3953-16.2017

Hibino, H., Fujita, A., Iwai, K., Yamada, M., & Kurachi, Y. (2004). Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes. Journal of Biological Chemistry, 279(42), 44065-44073. https://doi.org/10.1074/jbc.M405985200

Hol, E. M., & Pekny, M. (2015). Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Current Opinion in Cell Biology, 32, 121-130. https://doi.org/10.1016/j.ceb.2015.02.004

Hong, X., Jian, Y., Ding, S., Zhou, J., Zheng, X., Zhang, H., Zhou, B., Zhuang, C., Wan, J., & Tong, X. (2023). Kir4.1 channel activation in NG2 glia contributes to remyelination in ischemic stroke. eBioMedicine, 87, 104406. https://doi.org/10.1016/j.ebiom.2022.104406

Honsa, P., Pivonkova, H., Dzamba, D., Filipova, M., & Anderova, M. (2012). Polydendrocytes display large lineage plasticity following focal cerebral ischemia. PLoS One, 7(5), e36816. https://doi.org/10.1371/journal.pone.0036816

Honsa, P., Valny, M., Kriska, J., Matuskova, H., Harantova, L., Kirdajova, D., Valihrach, L., Androvic, P., Kubista, M., & Anderova, M. (2016). Generation of reactive astrocytes from NG2 cells is regulated by sonic hedgehog. Glia, 64(9), 1518-1531. https://doi.org/10.1002/glia.23019

Hrckulak, D., Kolar, M., Strnad, H., & Korinek, V. (2016). TCF/LEF transcription factors: An update from the internet resources. Cancers (Basel), 8(7), 70. https://doi.org/10.3390/cancers8070070

Huang, W., Bai, X., Stopper, L., Catalin, B., Cartarozzi, L. P., Scheller, A., & Kirchhoff, F. (2018). During development NG2 glial cells of the spinal cord are restricted to the oligodendrocyte lineage, but generate astrocytes upon acute injury. Neuroscience, 385, 154-165. https://doi.org/10.1016/j.neuroscience.2018.06.015

Huang, W., Zhao, N., Bai, X., Karram, K., Trotter, J., Goebbels, S., Scheller, A., & Kirchhoff, F. (2014). Novel NG2-CreERT2 knock-in mice demonstrate heterogeneous differentiation potential of NG2 glia during development. Glia, 62(6), 896-913. https://doi.org/10.1002/glia.22648

Hughes, E. G., Kang, S. H., Fukaya, M., & Bergles, D. E. (2013). Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nature Neuroscience, 16(6), 668-676. https://doi.org/10.1038/nn.3390

Jankowski, M. P., McIlwrath, S. L., Jing, X., Cornuet, P. K., Salerno, K. M., Koerber, H. R., & Albers, K. M. (2009). Sox11 transcription factor modulates peripheral nerve regeneration in adult mice. Brain Research, 1256, 43-54. https://doi.org/10.1016/j.brainres.2008.12.032

Jing, X., Wang, T., Huang, S., Glorioso, J. C., & Albers, K. M. (2012). The transcription factor Sox11 promotes nerve regeneration through activation of the regeneration-associated gene Sprr1a. Experimental Neurology, 233(1), 221-232. https://doi.org/10.1016/j.expneurol.2011.10.005

Kanazawa, Y., Makino, M., Morishima, Y., Yamada, K., Nabeshima, T., & Shirasaki, Y. (2008). Degradation of PEP-19, a calmodulin-binding protein, by calpain is implicated in neuronal cell death induced by intracellular Ca2+ overload. Neuroscience, 154(2), 473-481. https://doi.org/10.1016/j.neuroscience.2008.03.044

Kang, S. H., Fukaya, M., Yang, J. K., Rothstein, J. D., & Bergles, D. E. (2010). NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. Neuron, 68(4), 668-681. https://doi.org/10.1016/j.neuron.2010.09.009

Katan, M., & Luft, A. (2018). Global burden of stroke. Seminars in Neurology, 38(2), 208-211. https://doi.org/10.1055/s-0038-1649503

Khazaei, M. R., Halfter, H., Karimzadeh, F., Koo, J. H., Margolis, F. L., & Young, P. (2010). Bex1 is involved in the regeneration of axons after injury. Journal of Neurochemistry, 115(4), 910-920. https://doi.org/10.1111/j.1471-4159.2010.06960.x

Kim, E. J., Ables, J. L., Dickel, L. K., Eisch, A. J., & Johnson, J. E. (2011). Ascl1 (Mash1) defines cells with long-term neurogenic potential in subgranular and subventricular zones in adult mouse brain. PLoS One, 6(3), e18472. https://doi.org/10.1371/journal.pone.0018472

Kimura, M. T., Irie, S., Shoji-Hoshino, S., Mukai, J., Nadano, D., Oshimura, M., & Sato, T. A. (2001). 14-3-3 is involved in p75 neurotrophin receptor-mediated signal transduction. The Journal of Biological Chemistry, 276(20), 17291-17300. https://doi.org/10.1074/jbc.M005453200

Kirdajova, D., & Anderova, M. (2020). NG2 cells and their neurogenic potential. Current Opinion in Pharmacology, 50, 53-60. https://doi.org/10.1016/j.coph.2019.11.005

Kirdajova, D., Valihrach, L., Valny, M., Kriska, J., Krocianova, D., Benesova, S., Abaffy, P., Zucha, D., Klassen, R., Kolenicova, D., Honsa, P., Kubista, M., & Anderova, M. (2021). Transient astrocyte-like NG2 glia subpopulation emerges solely following permanent brain ischemia. Glia, 69(11), 2658-2681. https://doi.org/10.1002/glia.24064

Kiss, T., Nyul-Toth, A., Balasubramanian, P., Tarantini, S., Ahire, C., DelFavero, J., Yabluchanskiy, A., Csipo, T., Farkas, E., Wiley, G., Garman, L., Csiszar, A., & Ungvari, Z. (2020). Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain. Geroscience, 42(2), 429-444. https://doi.org/10.1007/s11357-020-00177-1

Kitazono, I., Hamada, T., Yoshimura, T., Kirishima, M., Yokoyama, S., Akahane, T., & Tanimoto, A. (2020). PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells. Laboratory Investigation, 100(12), 1551-1563. https://doi.org/10.1038/s41374-020-0462-z

Knotek, T., Janeckova, L., Kriska, J., Korinek, V., & Anderova, M. (2020). Glia and neural stem and progenitor cells of the healthy and ischemic brain: The workplace for the Wnt signaling pathway. Genes (Basel), 11(7), 804. https://doi.org/10.3390/genes11070804

Koo, J. H., Saraswati, M., & Margolis, F. L. (2005). Immunolocalization of Bex protein in the mouse brain and olfactory system. The Journal of Comparative Neurology, 487(1), 1-14. https://doi.org/10.1002/cne.20486

Koo, J. H., Smiley, M. A., Lovering, R. M., & Margolis, F. L. (2007). Bex1 knock out mice show altered skeletal muscle regeneration. Biochemical and Biophysical Research Communications, 363(2), 405-410. https://doi.org/10.1016/j.bbrc.2007.08.186

Kriska, J., Hermanova, Z., Knotek, T., Tureckova, J., & Anderova, M. (2021). On the common journey of neural cells through ischemic brain injury and Alzheimer's disease. International Journal of Molecular Sciences, 22(18), 9689. https://doi.org/10.3390/ijms22189689

Kriska, J., Janeckova, L., Kirdajova, D., Honsa, P., Knotek, T., Dzamba, D., Kolenicova, D., Butenko, O., Vojtechova, M., Capek, M., Kozmik, Z., Taketo, M. M., Korinek, V., & Anderova, M. (2021). Wnt/beta-catenin signaling promotes differentiation of ischemia-activated adult neural stem/progenitor cells to neuronal precursors. Frontiers in Neuroscience, 15, 628983. https://doi.org/10.3389/fnins.2021.628983

Kuleshov, M. V., Jones, M. R., Rouillard, A. D., Fernandez, N. F., Duan, Q., Wang, Z., Koplev, S., Jenkins, S. L., Jagodnik, K. M., Lachmann, A., McDermott, M. G., Monteiro, C. D., Gundersen, G. W., & Ma'ayan, A. (2016). Enrichr: A comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Research, 44(W1), W90-W97. https://doi.org/10.1093/nar/gkw377

Lang, J., Maeda, Y., Bannerman, P., Xu, J., Horiuchi, M., Pleasure, D., & Guo, F. (2013). Adenomatous polyposis coli regulates oligodendroglial development. The Journal of Neuroscience, 33(7), 3113-3130. https://doi.org/10.1523/JNEUROSCI.3467-12.2013

Larson, V. A., Mironova, Y., Vanderpool, K. G., Waisman, A., Rash, J. E., Agarwal, A., & Bergles, D. E. (2018). Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility. eLife, 7, e34829. https://doi.org/10.7554/eLife.34829

Larson, V. A., Zhang, Y., & Bergles, D. E. (2016). Electrophysiological properties of NG2(+) cells: Matching physiological studies with gene expression profiles. Brain Research, 1638(Pt B), 138-160. https://doi.org/10.1016/j.brainres.2015.09.010

Li, R., Zhang, P., Zhang, M., & Yao, Z. (2020). The roles of neuron-NG2 glia synapses in promoting oligodendrocyte development and remyelination. Cell and Tissue Research, 381(1), 43-53. https://doi.org/10.1007/s00441-020-03195-9

Li, Y., Wang, J., Zheng, Y., Zhao, Y., Guo, M., Li, Y., Bao, Q., Zhang, Y., Yang, L., & Li, Q. (2012). Sox11 modulates neocortical development by regulating the proliferation and neuronal differentiation of cortical intermediate precursors. Acta Biochimica et Biophysica Sinica (Shanghai), 44(8), 660-668. https://doi.org/10.1093/abbs/gms045

Lillien, L. E., Sendtner, M., & Raff, M. C. (1990). Extracellular matrix-associated molecules collaborate with ciliary neurotrophic factor to induce type-2 astrocyte development. The Journal of Cell Biology, 111(2), 635-644. https://doi.org/10.1083/jcb.111.2.635

Lin, S. C., & Bergles, D. E. (2004). Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nature Neuroscience, 7(1), 24-32. https://doi.org/10.1038/nn1162

Liu, L., McCullough, L., & Li, J. (2014). Genetic deletion of calcium/calmodulin-dependent protein kinase kinase beta (CaMKK beta) or CaMK IV exacerbates stroke outcomes in ovariectomized (OVXed) female mice. BMC Neuroscience, 15, 118. https://doi.org/10.1186/s12868-014-0118-2

Liu, Y., Miao, Q., Yuan, J., Han, S., Zhang, P., Li, S., Rao, Z., Zhao, W., Ye, Q., Geng, J., Zhang, X., & Cheng, L. (2015). Ascl1 converts dorsal midbrain astrocytes into functional neurons In vivo. The Journal of Neuroscience, 35(25), 9336-9355. https://doi.org/10.1523/JNEUROSCI.3975-14.2015

Liu, Z., Li, Y., Cui, Y., Roberts, C., Lu, M., Wilhelmsson, U., Pekny, M., & Chopp, M. (2014). Beneficial effects of gfap/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke. Glia, 62(12), 2022-2033. https://doi.org/10.1002/glia.22723

MacFarlane, S. N., & Sontheimer, H. (1997). Electrophysiological changes that accompany reactive gliosis in vitro. The Journal of Neuroscience, 17(19), 7316-7329. https://doi.org/10.1523/JNEUROSCI.17-19-07316.1997

MacFarlane, S. N., & Sontheimer, H. (2000). Changes in ion channel expression accompany cell cycle progression of spinal cord astrocytes. Glia, 30(1), 39-48. https://doi.org/10.1002/(sici)1098-1136(200003)30:1<39::aid-glia5>3.0.co;2-s

MacKay, H., Scott, C. A., Duryea, J. D., Baker, M. S., Laritsky, E., Elson, A. E., Garland, T., Jr., Fiorotto, M. L., Chen, R., Li, Y., Coarfa, C., Simerly, R. B., & Waterland, R. A. (2019). DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice. Nature Communications, 10(1), 5364. https://doi.org/10.1038/s41467-019-13339-3

Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., Lein, E. S., & Zeng, H. (2010). A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nature Neuroscience, 13(1), 133-140. https://doi.org/10.1038/nn.2467

Maglione, M., Tress, O., Haas, B., Karram, K., Trotter, J., Willecke, K., & Kettenmann, H. (2010). Oligodendrocytes in mouse corpus callosum are coupled via gap junction channels formed by connexin47 and connexin32. Glia, 58(9), 1104-1117. https://doi.org/10.1002/glia.20991

Martens, M., Ammar, A., Riutta, A., Waagmeester, A., Slenter, D. N., Hanspers, K., Miller, R., Digles, D., Lopes, E. N., Ehrhart, F., Dupuis, L. J., Winckers, L. A., Coort, S. L., Willighagen, E. L., Evelo, C. T., Pico, A. R., & Kutmon, M. (2021). WikiPathways: Connecting communities. Nucleic Acids Research, 49(D1), D613-D621. https://doi.org/10.1093/nar/gkaa1024

McCullough, L. D., Tarabishy, S., Liu, L., Benashski, S., Xu, Y., Ribar, T., Means, A., & Li, J. (2013). Inhibition of calcium/calmodulin-dependent protein kinase kinase beta and calcium/calmodulin-dependent protein kinase IV is detrimental in cerebral ischemia. Stroke, 44(9), 2559-2566. https://doi.org/10.1161/STROKEAHA.113.001030

Mignone, J. L., Kukekov, V., Chiang, A. S., Steindler, D., & Enikolopov, G. (2004). Neural stem and progenitor cells in nestin-GFP transgenic mice. The Journal of Comparative Neurology, 469(3), 311-324. https://doi.org/10.1002/cne.10964

Mizrak, D., Levitin, H. M., Delgado, A. C., Crotet, V., Yuan, J., Chaker, Z., Silva-Vargas, V., Sims, P. A., & Doetsch, F. (2019). Single-cell analysis of regional differences in adult V-SVZ neural stem cell lineages. Cell Reports, 26(2), 394-406e5. https://doi.org/10.1016/j.celrep.2018.12.044

Mouton-Liger, F., Thomas, S., Rattenbach, R., Magnol, L., Larigaldie, V., Ledru, A., Herault, Y., Verney, C., & Creau, N. (2011). PCP4 (PEP19) overexpression induces premature neuronal differentiation associated with Ca(2+) /calmodulin-dependent kinase II-delta activation in mouse models of Down syndrome. The Journal of Comparative Neurology, 519(14), 2779-2802. https://doi.org/10.1002/cne.22651

Mullen, R. J., Buck, C. R., & Smith, A. M. (1992). Neun, a neuronal specific nuclear-protein in vertebrates. Development, 116(1), 201-211.

Nakatani, H., Martin, E., Hassani, H., Clavairoly, A., Maire, C. L., Viadieu, A., Kerninon, C., Delmasure, A., Frah, M., Weber, M., Nakafuku, M., Zalc, B., Thomas, J. L., Guillemot, F., Nait-Oumesmar, B., & Parras, C. (2013). Ascl1/Mash1 promotes brain oligodendrogenesis during myelination and remyelination. The Journal of Neuroscience, 33(23), 9752-9768. https://doi.org/10.1523/JNEUROSCI.0805-13.2013

Neusch, C., Rozengurt, N., Jacobs, R. E., Lester, H. A., & Kofuji, P. (2001). Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. Journal of Neuroscience, 21(15), 5429-5438. https://doi.org/10.1523/Jneurosci.21-15-05429.2001

Nishiyama, A., Boshans, L., Goncalves, C. M., Wegrzyn, J., & Patel, K. D. (2016). Lineage, fate, and fate potential of NG2-glia. Brain Research, 1638(Pt B), 116-128. https://doi.org/10.1016/j.brainres.2015.08.013

Nishiyama, A., Chang, A., & Trapp, B. D. (1999). NG2+ glial cells: A novel glial cell population in the adult brain. Journal of Neuropathology and Experimental Neurology, 58(11), 1113-1124. https://doi.org/10.1097/00005072-199911000-00001

Olsen, T. S., Dehlendorff, C., & Andersen, K. K. (2007). Sex-related time-dependent variations in post-stroke survival: Evidence of a female stroke survival advantage. Neuroepidemiology, 29(3-4), 218-225. https://doi.org/10.1159/000112464

Pivonkova, H., Benesova, J., Butenko, O., Chvatal, A., & Anderova, M. (2010). Impact of global cerebral ischemia on K+ channel expression and membrane properties of glial cells in the rat hippocampus. Neurochemistry International, 57(7), 783-794. https://doi.org/10.1016/j.neuint.2010.08.016

Potzner, M. R., Griffel, C., Lutjen-Drecoll, E., Bosl, M. R., Wegner, M., & Sock, E. (2007). Prolonged Sox4 expression in oligodendrocytes interferes with normal myelination in the central nervous system. Molecular and Cellular Biology, 27(15), 5316-5326. https://doi.org/10.1128/MCB.00339-07

Psachoulia, K., Jamen, F., Young, K. M., & Richardson, W. D. (2009). Cell cycle dynamics of NG2 cells in the postnatal and ageing brain. Neuron Glia Biology, 5(3-4), 57-67. https://doi.org/10.1017/S1740925X09990354

Putkey, J. A., Waxham, M. N., Gaertner, T. R., Brewer, K. J., Goldsmith, M., Kubota, Y., & Kleerekoper, Q. K. (2008). Acidic/IQ motif regulator of calmodulin. The Journal of Biological Chemistry, 283(3), 1401-1410. https://doi.org/10.1074/jbc.M703831200

Rabinstein, A. A. (2017). Treatment of acute ischemic stroke. Continuum: Lifelong Learning in Neurology, 23, 62-81. https://doi.org/10.1212/CON.0000000000000420

Raff, M. C., Miller, R. H., & Noble, M. (1983). A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature, 303(5916), 390-396. https://doi.org/10.1038/303390a0

Robins, S. C., Trudel, E., Rotondi, O., Liu, X., Djogo, T., Kryzskaya, D., Bourque, C. W., & Kokoeva, M. V. (2013). Evidence for NG2-glia derived, adult-born functional neurons in the hypothalamus. PLoS One, 8(10), e78236. https://doi.org/10.1371/journal.pone.0078236

Robins, S. C., Villemain, A., Liu, X., Djogo, T., Kryzskaya, D., Storch, K. F., & Kokoeva, M. V. (2013). Extensive regenerative plasticity among adult NG2-glia populations is exclusively based on self-renewal. Glia, 61(10), 1735-1747. https://doi.org/10.1002/glia.22554

Schirmer, L., Mobius, W., Zhao, C., Cruz-Herranz, A., Ben Haim, L., Cordano, C., Shiow, L. R., Kelley, K. W., Sadowski, B., Timmons, G., Probstel, A. K., Wright, J. N., Sin, J. H., Devereux, M., Morrison, D. E., Chang, S. M., Sabeur, K., Green, A. J., Nave, K. A., … Rowitch, D. H. (2018). Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity. eLife, 7, e36428. https://doi.org/10.7554/eLife.36428

Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012). NIH image to ImageJ: 25 years of image analysis. Nature Methods, 9(7), 671-675. https://doi.org/10.1038/nmeth.2089

Seri, B., Garcia-Verdugo, J. M., McEwen, B. S., & Alvarez-Buylla, A. (2001). Astrocytes give rise to new neurons in the adult mammalian hippocampus. The Journal of Neuroscience, 21(18), 7153-7160. https://doi.org/10.1523/JNEUROSCI.21-18-07153.2001

Simon, C., Gotz, M., & Dimou, L. (2011). Progenitors in the adult cerebral cortex: Cell cycle properties and regulation by physiological stimuli and injury. Glia, 59(6), 869-881. https://doi.org/10.1002/glia.21156

Song, F., Hong, X., Cao, J., Ma, G., Han, Y., Cepeda, C., Kang, Z., Xu, T., Duan, S., Wan, J., & Tong, X. (2018). Kir4.1 channels in NG2-glia play a role in development, potassium signaling, and ischemia-related myelin loss. Communications Biology, 1, 80. https://doi.org/10.1038/s42003-018-0083-x

Song, F. E., Huang, J. L., Lin, S. H., Wang, S., Ma, G. F., & Tong, X. P. (2017). Roles of NG2-glia in ischemic stroke. CNS Neuroscience & Therapeutics, 23(7), 547-553. https://doi.org/10.1111/cns.12690

Stoeber, K., Tlsty, T. D., Happerfield, L., Thomas, G. A., Romanov, S., Bobrow, L., Williams, E. D., & Williams, G. H. (2001). DNA replication licensing and human cell proliferation. Journal of Cell Science, 114(Pt 11), 2027-2041. https://doi.org/10.1242/jcs.114.11.2027

Struebing, F. L., Wang, J., Li, Y., King, R., Mistretta, O. C., English, A. W., & Geisert, E. E. (2017). Differential expression of Sox11 and Bdnf mRNA isoforms in the injured and regenerating nervous systems. Frontiers in Molecular Neuroscience, 10, 354. https://doi.org/10.3389/fnmol.2017.00354

Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., 3rd, Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019). Comprehensive integration of single-cell data. Cell, 177(7), 1888-1902e21. https://doi.org/10.1016/j.cell.2019.05.031

Sueda, R., Imayoshi, I., Harima, Y., & Kageyama, R. (2019). High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain. Genes & Development, 33(9-10), 511-523. https://doi.org/10.1101/gad.323196.118

Sueda, R., & Kageyama, R. (2021). Oscillatory expression of Ascl1 in oligodendrogenesis. Gene Expression Patterns, 41, 119198. https://doi.org/10.1016/j.gep.2021.119198

Swiss, V. A., Nguyen, T., Dugas, J., Ibrahim, A., Barres, B., Androulakis, I. P., & Casaccia, P. (2011). Identification of a gene regulatory network necessary for the initiation of oligodendrocyte differentiation. PLoS One, 6(4), e18088. https://doi.org/10.1371/journal.pone.0018088

Tai, W., Wu, W., Wang, L. L., Ni, H., Chen, C., Yang, J., Zang, T., Zou, Y., Xu, X. M., & Zhang, C. L. (2021). In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury. Cell Stem Cell, 28(5), 923-937e4. https://doi.org/10.1016/j.stem.2021.02.009

Tamura, Y., Kataoka, Y., Cui, Y., Takamori, Y., Watanabe, Y., & Yamada, H. (2007). Multi-directional differentiation of doublecortin- and NG2-immunopositive progenitor cells in the adult rat neocortex in vivo. The European Journal of Neuroscience, 25(12), 3489-3498. https://doi.org/10.1111/j.1460-9568.2007.05617.x

Tan, C. L., Plotkin, J. L., Veno, M. T., von Schimmelmann, M., Feinberg, P., Mann, S., Handler, A., Kjems, J., Surmeier, D. J., O'Carroll, D., Greengard, P., & Schaefer, A. (2013). MicroRNA-128 governs neuronal excitability and motor behavior in mice. Science, 342(6163), 1254-1258. https://doi.org/10.1126/science.1244193

Tanner, D. C., Cherry, J. D., & Mayer-Proschel, M. (2011). Oligodendrocyte progenitors reversibly exit the cell cycle and give rise to astrocytes in response to interferon-gamma. The Journal of Neuroscience, 31(16), 6235-6246. https://doi.org/10.1523/JNEUROSCI.5905-10.2011

Ulbricht, E., Pannicke, T., Hollborn, M., Raap, M., Goczalik, I., Iandiev, I., Hartig, W., Uhlmann, S., Wiedemann, P., Reichenbach, A., Bringmann, A., & Francke, M. (2008). Proliferative gliosis causes mislocation and inactivation of inwardly rectifying K(+) (Kir) channels in rabbit retinal glial cells. Experimental Eye Research, 86(2), 305-313. https://doi.org/10.1016/j.exer.2007.11.002

Valny, M., Honsa, P., Waloschkova, E., Matuskova, H., Kriska, J., Kirdajova, D., Androvic, P., Valihrach, L., Kubista, M., & Anderova, M. (2018). A single-cell analysis reveals multiple roles of oligodendroglial lineage cells during post-ischemic regeneration. Glia, 66(5), 1068-1081. https://doi.org/10.1002/glia.23301

Vasconcelos, F. F., & Castro, D. S. (2014). Transcriptional control of vertebrate neurogenesis by the proneural factor Ascl1. Frontiers in Cellular Neuroscience, 8, 412. https://doi.org/10.3389/fncel.2014.00412

Vierbuchen, T., Ostermeier, A., Pang, Z. P., Kokubu, Y., Sudhof, T. C., & Wernig, M. (2010). Direct conversion of fibroblasts to functional neurons by defined factors. Nature, 463(7284), 1035-1041. https://doi.org/10.1038/nature08797

Vigano, F., Schneider, S., Cimino, M., Bonfanti, E., Gelosa, P., Sironi, L., Abbracchio, M. P., & Dimou, L. (2016). GPR17 expressing NG2-glia: Oligodendrocyte progenitors serving as a reserve pool after injury. Glia, 64(2), 287-299. https://doi.org/10.1002/glia.22929

Vilar, M., Murillo-Carretero, M., Mira, H., Magnusson, K., Besset, V., & Ibanez, C. F. (2006). Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle. The EMBO Journal, 25(6), 1219-1230. https://doi.org/10.1038/sj.emboj.7601017

Virani, S. S., Alonso, A., Aparicio, H. J., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Cheng, S., Delling, F. N., Elkind, M. S. V., Evenson, K. R., Ferguson, J. F., Gupta, D. K., Khan, S. S., Kissela, B. M., Knutson, K. L., Lee, C. D., Lewis, T. T., … Epidemiology American Heart Association Council on, Committee Prevention Statistics, and Subcommittee Stroke Statistics. (2021). Heart disease and stroke Statistics-2021 update: A report from the American Heart Association. Circulation, 143(8), e254-e743. https://doi.org/10.1161/CIR.0000000000000950

Wang, X., Karlsson, J. O., Zhu, C., Bahr, B. A., Hagberg, H., & Blomgren, K. (2001). Caspase-3 activation after neonatal rat cerebral hypoxia-ischemia. Biology of the Neonate, 79(3-4), 172-179. https://doi.org/10.1159/000047087

Wang, Y., Lin, L., Lai, H., Parada, L. F., & Lei, L. (2013). Transcription factor Sox11 is essential for both embryonic and adult neurogenesis. Developmental Dynamics, 242(6), 638-653. https://doi.org/10.1002/dvdy.23962

Wharton, S. B., Chan, K. K., Anderson, J. R., Stoeber, K., & Williams, G. H. (2001). Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki67 labelling index, histological grade and prognosis. Neuropathology and Applied Neurobiology, 27(4), 305-313. https://doi.org/10.1046/j.0305-1846.2001.00333.x

Wilhelmsson, U., Pozo-Rodrigalvarez, A., Kalm, M., de Pablo, Y., Widestrand, A., Pekna, M., & Pekny, M. (2019). The role of GFAP and vimentin in learning and memory. Biological Chemistry, 400(9), 1147-1156. https://doi.org/10.1515/hsz-2019-0199

Wilson, H. C., Scolding, N. J., & Raine, C. S. (2006). Co-expression of PDGF alpha receptor and NG2 by oligodendrocyte precursors in human CNS and multiple sclerosis lesions. Journal of Neuroimmunology, 176(1-2), 162-173. https://doi.org/10.1016/j.jneuroim.2006.04.014

Xie, Z., Bailey, A., Kuleshov, M. V., Clarke, D. J. B., Evangelista, J. E., Jenkins, S. L., Lachmann, A., Wojciechowicz, M. L., Kropiwnicki, E., Jagodnik, K. M., Jeon, M., & Ma'ayan, A. (2021). Gene set knowledge discovery with Enrichr. Current Protocols, 1(3), e90. https://doi.org/10.1002/cpz1.90

Yang, Q. K., Xiong, J. X., & Yao, Z. X. (2013). Neuron-NG2 cell synapses: Novel functions for regulating NG2 cell proliferation and differentiation. BioMed Research International, 2013, 402843. https://doi.org/10.1155/2013/402843

Young, K. M., Psachoulia, K., Tripathi, R. B., Dunn, S. J., Cossell, L., Attwell, D., Tohyama, K., & Richardson, W. D. (2013). Oligodendrocyte dynamics in the healthy adult CNS: Evidence for myelin remodeling. Neuron, 77(5), 873-885. https://doi.org/10.1016/j.neuron.2013.01.006

Yu, Y., Chen, Y., Kim, B., Wang, H., Zhao, C., He, X., Liu, L., Liu, W., Wu, L. M., Mao, M., Chan, J. R., Wu, J., & Lu, Q. R. (2013). Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell, 152(1-2), 248-261. https://doi.org/10.1016/j.cell.2012.12.006

Zawadzka, M., Rivers, L. E., Fancy, S. P., Zhao, C., Tripathi, R., Jamen, F., Young, K., Goncharevich, A., Pohl, H., Rizzi, M., Rowitch, D. H., Kessaris, N., Suter, U., Richardson, W. D., & Franklin, R. J. (2010). CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem Cell, 6(6), 578-590. https://doi.org/10.1016/j.stem.2010.04.002

Zeisel, A., Munoz-Manchado, A. B., Codeluppi, S., Lonnerberg, P., La Manno, G., Jureus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., Rolny, C., Castelo-Branco, G., Hjerling-Leffler, J., & Linnarsson, S. (2015). Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science, 347(6226), 1138-1142. https://doi.org/10.1126/science.aaa1934

Zhang, S., Yan, L., Cui, C., Wang, Z., Wu, J., Lv, A., Zhao, M., Dong, B., Zhang, W., Guan, X., Tian, X., & Hao, C. (2020). Downregulation of RRM2 attenuates retroperitoneal liposarcoma progression via the Akt/mTOR/4EBP1 pathway: Clinical, biological, and therapeutic significance. Oncotargets and Therapy, 13, 6523-6537. https://doi.org/10.2147/OTT.S246613

Zhang, X., Lan, Y., Xu, J., Quan, F., Zhao, E., Deng, C., Luo, T., Xu, L., Liao, G., Yan, M., Ping, Y., Li, F., Shi, A., Bai, J., Zhao, T., Li, X., & Xiao, Y. (2019). CellMarker: A manually curated resource of cell markers in human and mouse. Nucleic Acids Research, 47(D1), D721-D728. https://doi.org/10.1093/nar/gky900

Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., Deng, S., Liddelow, S. A., Zhang, C., Daneman, R., Maniatis, T., Barres, B. A., & Wu, J. Q. (2014). An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. The Journal of Neuroscience, 34(36), 11929-11947. https://doi.org/10.1523/JNEUROSCI.1860-14.2014

Zhao, C., Deng, Y., Liu, L., Yu, K., Zhang, L., Wang, H., He, X., Wang, J., Lu, C., Wu, L. N., Weng, Q., Mao, M., Li, J., van Es, J. H., Xin, M., Parry, L., Goldman, S. A., Clevers, H., & Lu, Q. R. (2016). Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation. Nature Communications, 7, 10883. https://doi.org/10.1038/ncomms10883

Zhou, M., Schools, G. P., & Kimelberg, H. K. (2006). Development of GLAST(+) astrocytes and NG2(+) glia in rat hippocampus CA1: Mature astrocytes are electrophysiologically passive. Journal of Neurophysiology, 95(1), 134-143. https://doi.org/10.1152/jn.00570.2005

Zhu, S., Chen, M., Ying, Y., Wu, Q., Huang, Z., Ni, W., Wang, X., Xu, H., Bennett, S., Xiao, J., & Xu, J. (2022). Versatile subtypes of pericytes and their roles in spinal cord injury repair, bone development and repair. Bone Research, 10(1), 30. https://doi.org/10.1038/s41413-022-00203-2

Zhu, X., Hill, R. A., Dietrich, D., Komitova, M., Suzuki, R., & Nishiyama, A. (2011). Age-dependent fate and lineage restriction of single NG2 cells. Development, 138(4), 745-753. https://doi.org/10.1242/dev.047951

Zhu, X. Q., Bergles, D. E., & Nishiyama, A. (2008). NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development, 135(1), 145-157. https://doi.org/10.1242/dev.004895

Spatiotemporal transcriptomic map of glial cell response in a mouse model of acute brain ischemia