Transcription factors belonging to the basic helix-loop-helix (bHLH) family are key regulators of cell fate specification and differentiation during development. Their dysregulation is implicated not only in developmental abnormalities but also in various adult diseases and cancers. Recently, the abilities of bHLH factors have been exploited in reprogramming strategies for cell replacement therapy. One such factor is NEUROD1, which has been associated with the reprogramming of the epigenetic landscape and potentially possessing pioneer factor abilities, initiating neuronal developmental programs, and enforcing pancreatic endocrine differentiation. The review aims to consolidate current knowledge on NEUROD1's multifaceted roles and mechanistic pathways in human and mouse cell differentiation and reprogramming, exploring NEUROD1 roles in guiding the development and reprogramming of neuroendocrine cell lineages. The review focuses on NEUROD1's molecular mechanisms, its interactions with other transcription factors, its role as a pioneer factor in chromatin remodeling, and its potential in cell reprogramming. We also show a differential potential of NEUROD1 in differentiation of neurons and pancreatic endocrine cells, highlighting its therapeutic potential and the necessity for further research to fully understand and utilize its capabilities.

Laboratory of Molecular Pathogenetics Institute of Biotechnology Czech Academy of Sciences Vestec Czechia

Zobrazit více v PubMed

Akol I., Izzo A., Gather F., Strack S., Heidrich S., hAilín D. Ó., et al. (2023). Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome. Proc. Natl. Acad. Sci. 120 (2), e2122467120. 10.1073/pnas.2122467120 PubMed DOI PMC

Atchley W. R., Fitch W. M. (1997). A natural classification of the basic helix-loop-helix class of transcription factors. Proc. Natl. Acad. Sci. U. S. A. 94 (10), 5172–5176. 10.1073/pnas.94.10.5172 PubMed DOI PMC

Baker N. E., Brown N. L. (2018). All in the family: proneural bHLH genes and neuronal diversity. Development 145 (9), dev159426. 10.1242/dev.159426 PubMed DOI PMC

Barazeghi E., Hellman P., Norlén O., Westin G., Stålberg P. (2021). EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine. Sci. Rep. 11 (1), 22733. 10.1038/s41598-021-02181-7 PubMed DOI PMC

Bertrand N., Castro D. S., Guillemot F. (2002). Proneural genes and the specification of neural cell types. Nat. Rev. Neurosci. 3 (7), 517–530. 10.1038/nrn874 PubMed DOI

Bohuslavova R., Fabriciova V., Smolik O., Lebron-Mora L., Abaffy P., Benesova S., et al. (2023). NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development. Nat. Commun. 14 (1), 5554. 10.1038/s41467-023-41306-6 PubMed DOI PMC

Bohuslavova R., Smolik O., Malfatti J., Berkova Z., Novakova Z., Saudek F., et al. (2021). NEUROD1 is required for the early α and β endocrine differentiation in the pancreas. Int. J. Mol. Sci. 22 (13), 6713. 10.3390/ijms22136713 PubMed DOI PMC

Brulet R., Matsuda T., Zhang L., Miranda C., Giacca M., Kaspar B. K., et al. (2017). NEUROD1 instructs neuronal conversion in non-reactive astrocytes. Stem Cell. Rep. 8 (6), 1506–1515. 10.1016/j.stemcr.2017.04.013 PubMed DOI PMC

Bysani M., Agren R., Davegårdh C., Volkov P., Rönn T., Unneberg P., et al. (2019). ATAC-seq reveals alterations in open chromatin in pancreatic islets from subjects with type 2 diabetes. Sci. Rep. 9, 7785. 10.1038/s41598-019-44076-8 PubMed DOI PMC

Casey B. H., Kollipara R. K., Pozo K., Johnson J. E. (2018). Intrinsic DNA binding properties demonstrated for lineage-specifying basic helix-loop-helix transcription factors. Genome Res. 28 (4), 484–496. 10.1101/gr.224360.117 PubMed DOI PMC

Cejas P., Xie Y., Font-Tello A., Lim K., Syamala S., Qiu X., et al. (2021). Subtype heterogeneity and epigenetic convergence in neuroendocrine prostate cancer. Nat. Commun. 12 (1), 5775. 10.1038/s41467-021-26042-z PubMed DOI PMC

Chakraborty G., Gupta K., Kyprianou N. (2023). Epigenetic mechanisms underlying subtype heterogeneity and tumor recurrence in prostate cancer. Nat. Commun. 14 (1), 567. 10.1038/s41467-023-36253-1 PubMed DOI PMC

Chao C. S., Loomis Z. L., Lee J. E., Sussel L. (2007). Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells. Dev. Biol. 312 (2), 523–532. 10.1016/j.ydbio.2007.09.057 PubMed DOI PMC

Cheng Y., Liao S., Xu G., Hu J., Guo D., Du F., et al. (2020). NeuroD1 dictates tumor cell differentiation in medulloblastoma. Cell. Rep. 31 (12), 107782. 10.1016/j.celrep.2020.107782 PubMed DOI PMC

Choi W.-Y., Hwang J.-H., Cho A.-Na, Lee A. J., Jung I., Cho S.-W., et al. (2020). NEUROD1 intrinsically initiates differentiation of induced pluripotent stem cells into neural progenitor cells. Mol. Cells 43 (12), 1011–1022. 10.14348/molcells.2020.0207 PubMed DOI PMC

Chu K., Nemoz-Gaillard E., Tsai M. J. (2001). BETA2 and pancreatic islet development. Recent Prog. Hormone Res. 56, 23–46. 10.1210/rp.56.1.23 PubMed DOI

Cindolo L., Franco R., Cantile M., Schiavo G., Liguori G., Chiodini P., et al. (2007). NeuroD1 expression in human prostate cancer: can it contribute to neuroendocrine differentiation comprehension? Eur. Urol. 52 (5), 1365–1373. 10.1016/j.eururo.2006.11.030 PubMed DOI

Crews S. T., Fan C. M. (1999). Remembrance of things PAS: regulation of development by bHLH-PAS proteins. Curr. Opin. Genet. Dev. 9 (5), 580–587. 10.1016/s0959-437x(99)00003-9 PubMed DOI

Davies A., Zoubeidi A., Selth L. A. (2020). The epigenetic and transcriptional landscape of neuroendocrine prostate cancer. Endocr. Relat. Cancer 27 (2), R35–R50. 10.1530/ERC-19-0420 PubMed DOI

de Martin X., Sodaei R., Santpere G. (2021). Mechanisms of binding specificity among bHLH transcription factors. Int. J. Mol. Sci. 22 (17), 9150. 10.3390/ijms22179150 PubMed DOI PMC

Dennis D. J., Han S., Schuurmans C. (2019). bHLH transcription factors in neural development, disease, and reprogramming. Brain Res. 1705, 48–65. 10.1016/j.brainres.2018.03.013 PubMed DOI

Dudek K. D., Osipovich A. B., Cartailler J.-P., Gu G., Magnuson M. A. (2021). Insm1, Neurod1, and Pax6 promote murine pancreatic endocrine cell development through overlapping yet distinct RNA transcription and splicing programs. G3 Genes|Genomes|Genetics 11 (11), jkab303. 10.1093/g3journal/jkab303 PubMed DOI PMC

Filova I., Bohuslavova R., Tavakoli M., Yamoah E. N., Fritzsch B., Pavlinkova G. (2022). Early deletion of Neurod1 alters neuronal lineage potential and diminishes neurogenesis in the inner ear. Front. Cell. Dev. Biol. 10, 845461. 10.3389/fcell.2022.845461 PubMed DOI PMC

Fritzsch B., Jahan I., Pan N., Elliott K. L. (2015). Evolving gene regulatory networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system. Cell. Tissue Res. 359 (1), 295–313. 10.1007/s00441-014-2043-1 PubMed DOI PMC

Gao Z., Ure K., Ables J. L., Lagace D. C., Nave K. A., Goebbels S., et al. (2009). Neurod1 is essential for the survival and maturation of adult-born neurons. Nat. Neurosci. 12 (9), 1090–1092. 10.1038/nn.2385 PubMed DOI PMC

Gerace D., Martiniello-Wilks R., Habib R., Ren B., Nassif N. T., O’Brien B. A., et al. (2019). Ex vivo expansion of murine MSC impairs transcription factor-induced differentiation into pancreatic β-cells. Stem Cells Int. 2019, 1–15. 10.1155/2019/1395301 PubMed DOI PMC

Gong L., Yan Q., Zhang Y., Fang X., Liu B., Guan X. (2019). Cancer cell reprogramming: a promising therapy converting malignancy to benignity. Cancer Commun. (Lond) 39 (1), 48. 10.1186/s40880-019-0393-5 PubMed DOI PMC

Graca I., Pereira-Silva E., Henrique R., Packham G., Crabb S. J., Jeronimo C. (2016). Epigenetic modulators as therapeutic targets in prostate cancer. Clin. Epigenetics 8, 98. 10.1186/s13148-016-0264-8 PubMed DOI PMC

Gu C., Stein G. H., Pan N., Goebbels S., Hörnberg H., Nave K.-A., et al. (2010). Pancreatic beta cells require NeuroD to achieve and maintain functional maturity. Cell. Metab. 11 (4), 298–310. 10.1016/j.cmet.2010.03.006 PubMed DOI PMC

Guo Q. S., Zhu M. Y., Wang L., Fan X. J., Lu Y. H., Wang Z. W., et al. (2012). Combined transfection of the three transcriptional factors, PDX-1, NeuroD1, and MafA, causes differentiation of bone marrow mesenchymal stem cells into insulin-producing cells. Exp. Diabetes Res. 2012, 672013. 10.1155/2012/672013 PubMed DOI PMC

Guo Z., Zhang L., Wu Z., Chen Y., Wang F., Chen G. (2014). In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model. Cell. Stem Cell. 14 (2), 188–202. 10.1016/j.stem.2013.12.001 PubMed DOI PMC

Hallam S., Singer E., Waring D., Jin Y. (2000). The C. elegans NeuroD homolog cnd-1 functions in multiple aspects of motor neuron fate specification. Development 127 (19), 4239–4252. 10.1242/dev.127.19.4239 PubMed DOI

Harikumar A., Meshorer E. (2015). Chromatin remodeling and bivalent histone modifications in embryonic stem cells. EMBO Rep. 16 (12), 1609–1619. 10.15252/embr.201541011 PubMed DOI PMC

Hevner R. F., Hodge R. D., Daza R. A., Englund C. (2006). Transcription factors in glutamatergic neurogenesis: conserved programs in neocortex, cerebellum, and adult hippocampus. Neurosci. Res. 55 (3), 223–233. 10.1016/j.neures.2006.03.004 PubMed DOI

Horikawa Y., Enya M. (2019). Genetic dissection and clinical features of MODY6 (NEUROD1-MODY). Curr. Diab Rep. 19 (3), 12. 10.1007/s11892-019-1130-9 PubMed DOI

Huang Y.-H., Klingbeil O., He X.-Y., Wu X. S., Arun G., Lu B., et al. (2018). POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer. Genes. & Dev. 32 (13-14), 915–928. 10.1101/gad.314815.118 PubMed DOI PMC

Ikematsu Y., Tanaka K., Toyokawa G., Ijichi K., Ando N., Yoneshima Y., et al. (2020). NEUROD1 is highly expressed in extensive-disease small cell lung cancer and promotes tumor cell migration. Lung Cancer 146, 97–104. 10.1016/j.lungcan.2020.05.012 PubMed DOI

Imayoshi I., Kageyama R. (2014). bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells. Neuron 82 (1), 9–23. 10.1016/j.neuron.2014.03.018 PubMed DOI

Ireland A. S., Micinski A. M., Kastner D. W., Guo B., Wait S. J., Spainhower K. B., et al. (2020). MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate. Cancer Cell. 38 (1), 60–78. 10.1016/j.ccell.2020.05.001 PubMed DOI PMC

Irie T., MatsudaIto-Ito K., Matsuda T., Masuda T., Prinz M., Isobe N., et al. (2023). Lineage tracing identifies in vitro microglia-to-neuron conversion by NeuroD1 expression. Genes. Cells. 28 (7), gtc.13033. 10.1111/gtc.13033 PubMed DOI PMC

Itkin-Ansari P., Marcora E., Geron I., Tyrberg B., Demeterco C., Hao E., et al. (2005). NeuroD1 in the endocrine pancreas: localization and dual function as an activator and repressor. Dev. Dyn. 233 (3), 946–953. 10.1002/dvdy.20443 PubMed DOI

Iwafuchi-Doi M., Zaret K. S. (2016). Cell fate control by pioneer transcription factors. Development 143 (11), 1833–1837. 10.1242/dev.133900 PubMed DOI PMC

Jahan I., Pan N., Kersigo J., Fritzsch B. (2010). Neurod1 suppresses hair cell differentiation in ear ganglia and regulates hair cell subtype development in the cochlea. PloS one 5 (7), e11661. 10.1371/journal.pone.0011661 PubMed DOI PMC

Jones S. (2004). An overview of the basic helix-loop-helix proteins. Genome Biol. 5 (6), 226. 10.1186/gb-2004-5-6-226 PubMed DOI PMC

Karpińska M., Czauderna M. (2022). Pancreas-its functions, disorders, and physiological impact on the mammals’ organism. Front. Physiol. 13, 807632. 10.3389/fphys.2022.807632 PubMed DOI PMC

Kim W.-Y., Fritzsch B., Serls A., Bakel L. A., Huang E. J., Reichardt L. F., et al. (2001). NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development. Development 128 (3), 417–426. 10.1242/dev.128.3.417 PubMed DOI PMC

Ledent V., Vervoort M. (2001). The basic helix-loop-helix protein family: comparative genomics and phylogenetic analysis. Genome Res. 11 (5), 754–770. 10.1101/gr.177001 PubMed DOI PMC

Lee J. E., Hollenberg S. M., Snider L., Turner D. L., Lipnick N., Weintraub H. (1995). Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. Science 268 (5212), 836–844. 10.1126/science.7754368 PubMed DOI

Lewis N. A., Klein R. H., Kelly C., Yee J., Knoepfler P. S. (2022). Histone H3.3 K27M chromatin functions implicate a network of neurodevelopmental factors including ASCL1 and NEUROD1 in DIPG. Epigenetics Chromatin 15 (1), 18. 10.1186/s13072-022-00447-6 PubMed DOI PMC

Li H.-Tu, Jiang F.-Xu, Shi P., Zhang T., Liu X.-Yu, Lin X.-W., et al. (2017). In vitro reprogramming of rat bmMSCs into pancreatic endocrine-like cells. Vitro Cell. Dev. Biol. - Animal 53 (2), 157–166. 10.1007/s11626-016-0087-0 PubMed DOI

Liu M., Pereira F. A., Price S. D., Chu M.-jin, Shope C., Himes D., et al. (2000b). Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems. Genes. & Dev. 14 (22), 2839–2854. 10.1101/gad.840500 PubMed DOI PMC

Liu M., Pleasure S. J., Collins A. E., Noebels J. L., Naya F. J., Tsai M. J., et al. (2000a). Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proc. Natl. Acad. Sci. U. S. A. 97 (2), 865–870. 10.1073/pnas.97.2.865 PubMed DOI PMC

Llabata P., Torres-Diz M., Gomez A., Tomas-Daza L., Romero O. A., Grego-Bessa J., et al. (2021). MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex. Proc. Natl. Acad. Sci. 118 (37), e2024824118. 10.1073/pnas.2024824118 PubMed DOI PMC

Ma A., Stratikopoulos E., Park K. S., Wei J., Martin T. C., Yang X., et al. (2020). Discovery of a first-in-class EZH2 selective degrader. Nat. Chem. Biol. 16 (2), 214–222. 10.1038/s41589-019-0421-4 PubMed DOI PMC

Macova I., Pysanenko K., Chumak T., Dvorakova M., Bohuslavova R., Syka J., et al. (2019). Neurod1 is essential for the primary tonotopic organization and related auditory information processing in the midbrain. J. Neurosci. 39 (6), 984–1004. 10.1523/JNEUROSCI.2557-18.2018 PubMed DOI PMC

Malecki M. T., Jhala U. S., Antonellis A., Fields L., Doria A., Orban T., et al. (1999). Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat. Genet. 23 (3), 323–328. 10.1038/15500 PubMed DOI

Mastracci T. L., Anderson K. R., Papizan J. B., Sussel L. (2013). Regulation of Neurod1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas. PLOS Genet. 9 (2), e1003278. 10.1371/journal.pgen.1003278 PubMed DOI PMC

Matsuda T., Irie T., Katsurabayashi S., Hayashi Y., Nagai T., Hamazaki N., et al. (2019). Pioneer factor NeuroD1 rearranges transcriptional and epigenetic profiles to execute microglia-neuron conversion. Neuron 101 (3), 472–485. 10.1016/j.neuron.2018.12.010 PubMed DOI

Matsuda-Ito K., Matsuda T., Nakashima K. (2022). Expression level of the reprogramming factor NeuroD1 is critical for neuronal conversion efficiency from different cell types. Sci. Rep. 12 (1), 17980. 10.1038/s41598-022-22802-z PubMed DOI PMC

Miyata T., Maeda T., Lee J. E. (1999). NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. Genes. Dev. 13 (13), 1647–1652. 10.1101/gad.13.13.1647 PubMed DOI PMC

Morrow E. M., Furukawa T., Lee J. E., Cepko C. L. (1999). NeuroD regulates multiple functions in the developing neural retina in rodent. Development 126 (1), 23–36. 10.1242/dev.126.1.23 PubMed DOI

Murre C. (2019). Helix-loop-helix proteins and the advent of cellular diversity: 30 years of discovery. Genes. Dev. 33 (1-2), 6–25. 10.1101/gad.320663.118 PubMed DOI PMC

Naya F. J., Huang H. P., Qiu Y., Mutoh H., DeMayo F. J., Leiter A. B., et al. (1997). Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes. Dev. 11 (18), 2323–2334. 10.1101/gad.11.18.2323 PubMed DOI PMC

Naya F. J., Stellrecht C. M., Tsai M. J. (1995). Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor. Genes. & Dev. 9 (8), 1009–1019. 10.1101/gad.9.8.1009 PubMed DOI

Neptune E. R., Podowski M., Calvi C., Cho J. H., Garcia J. G., Tuder R., et al. (2008). Targeted disruption of NeuroD, a proneural basic helix-loop-helix factor, impairs distal lung formation and neuroendocrine morphology in the neonatal lung. J. Biol. Chem. 283 (30), 21160–21169. 10.1074/jbc.M708692200 PubMed DOI PMC

Nishimura K., Weichert R. M., Liu W., Davis R. L., Dabdoub A. (2014). Generation of induced neurons by direct reprogramming in the mammalian cochlea. Neuroscience 275, 125–135. 10.1016/j.neuroscience.2014.05.067 PubMed DOI

Noda T., Meas S. J., Nogami J., Amemiya Y., Uchi R., Ohkawa Y., et al. (2018). Direct reprogramming of spiral ganglion non-neuronal cells into neurons: toward ameliorating sensorineural hearing loss by gene therapy. Front. Cell. Dev. Biol. 6, 16. 10.3389/fcell.2018.00016 PubMed DOI PMC

Oser M. G., Niederst M. J., Sequist L. V., Engelman J. A. (2015). Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 16 (4), e165–e172. 10.1016/S1470-2045(14)71180-5 PubMed DOI PMC

Packard A., Giel-Moloney M., Leiter A., Schwob J. E. (2011). Progenitor cell capacity of NeuroD1-expressing globose basal cells in the mouse olfactory epithelium. J. Comp. Neurol. 519 (17), 3580–3596. 10.1002/cne.22726 PubMed DOI PMC

Pan N., Jahan I., Lee J. E., Fritzsch B. (2009). Defects in the cerebella of conditional Neurod1 null mice correlate with effective Tg(Atoh1-cre) recombination and granule cell requirements for Neurod1 for differentiation. Cell. Tissue Res. 337 (3), 407–428. 10.1007/s00441-009-0826-6 PubMed DOI PMC

Pang Z. P., Yang N., Vierbuchen T., Ostermeier A., Fuentes D. R., Yang T. Q., et al. (2011). Induction of human neuronal cells by defined transcription factors. Nature 476 (7359), 220–223. 10.1038/nature10202 PubMed DOI PMC

Pataskar A., Jung J., Smialowski P., Noack F., Calegari F., Straub T., et al. (2016). NeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program. EMBO J. 35 (1), 24–45. 10.15252/embj.201591206 PubMed DOI PMC

Pennesi M. E., Cho J. H., Yang Z., Wu S. H., Zhang J., Wu S. M., et al. (2003). BETA2/NeuroD1 null mice: a new model for transcription factor-dependent photoreceptor degeneration. J. Neurosci. 23 (2), 453–461. 10.1523/JNEUROSCI.23-02-00453.2003 PubMed DOI PMC

Petersen G. F., Hilbert B. J., Trope G. D., Kalle W. H. J., Strappe P. M. (2015). Direct conversion of equine adipose-derived stem cells into induced neuronal cells is enhanced in three-dimensional culture. Cell. Reprogr. 17 (6), 419–426. 10.1089/cell.2015.0046 PubMed DOI

Pongor L. S., Tlemsani C., Elloumi F., Arakawa Y., Jo U., Gross J. M., et al. (2022). Integrative epigenomic analyses of small cell lung cancer cells demonstrates the clinical translational relevance of gene body methylation. iScience 25 (11), 105338. 10.1016/j.isci.2022.105338 PubMed DOI PMC

Pyott S. J., Pavlinkova G., Yamoah E. N., Fritzsch B. (2024). Harmony in the molecular orchestra of hearing: developmental mechanisms from the ear to the brain. Annu. Rev. Neurosci. 47. 10.1146/annurev-neuro-081423-093942 PubMed DOI PMC

Rao Y., Du S., Yang B., Wang Y., Li Y., Li R., et al. (2021). NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming. Neuron 109 (24), 4094–4108 e5. 10.1016/j.neuron.2021.11.008 PubMed DOI

Rao Y., Peng Bo. (2022). Failure of observing NeuroD1-induced microglia-to-neuron conversion in vitro is not attributed to the low NeuroD1 expression level. Mol. Brain 15 (1), 31. 10.1186/s13041-022-00912-z PubMed DOI PMC

Ren B., Tao C., Swan M. A., Joachim N., Martiniello-Wilks R., Nassif N. T., et al. (2016). Pancreatic transdifferentiation and glucose-regulated production of human insulin in the H4IIE rat liver cell line. Int. J. Mol. Sci. 17 (4), 534. 10.3390/ijms17040534 PubMed DOI PMC

Romer A. I., Singer R. A., Sui L., Egli D., Sussel L. (2019). Murine perinatal β-cell proliferation and the differentiation of human stem cell-derived insulin-expressing cells require NEUROD1. Diabetes 68 (12), 2259–2271. 10.2337/db19-0117 PubMed DOI PMC

Rotinen M., You S., Yang J., Coetzee S. G., Reis-Sobreiro M., Huang W.-C., et al. (2018). ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis. Nat. Med. 24 (12), 1887–1898. 10.1038/s41591-018-0241-1 PubMed DOI PMC

Rubio-Cabezas O., Minton J. A. L., Kantor I., Williams D., Ellard S., Hattersley A. T. (2010). Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes 59 (9), 2326–2331. 10.2337/db10-0011 PubMed DOI PMC

Schwab M. H., Bartholomae A., Heimrich B., Feldmeyer D., Druffel-Augustin S., Goebbels S., et al. (2000). Neuronal basic helix-loop-helix proteins (NEX and BETA2/Neuro D) regulate terminal granule cell differentiation in the hippocampus. J. Neurosci. 20 (10), 3714–3724. 10.1523/JNEUROSCI.20-10-03714.2000 PubMed DOI PMC

Seo S., Richardson G. A., Kroll K. L. (2005). The SWI/SNF chromatin remodeling protein Brg1 is required for vertebrate neurogenesis and mediates transactivation of Ngn and NeuroD. Development 132 (1), 105–115. 10.1242/dev.01548 PubMed DOI

Singh A., Mahesh A., Noack F., Cardoso De Toledo B., Calegari F., Tiwari V. K. (2022). Tcf12 and NeuroD1 cooperatively drive neuronal migration during cortical development. Development 149 (3), dev200250. 10.1242/dev.200250 PubMed DOI PMC

Sommer L., Ma Q., Anderson D. J. (1996). neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS. Mol. Cell. Neurosci. 8 (4), 221–241. 10.1006/mcne.1996.0060 PubMed DOI

Son E. Y., Ichida J. K., Wainger B. J., Toma J. S., Rafuse V. F., Woolf C. J., et al. (2011). Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell. Stem Cell. 9 (3), 205–218. 10.1016/j.stem.2011.07.014 PubMed DOI PMC

Sugimori M., Nagao M., Bertrand N., Parras C. M., Guillemot F., Nakafuku M. (2007). Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord. Development 134 (8), 1617–1629. 10.1242/dev.001255 PubMed DOI

Vermeiren S., Bellefroid E. J., Desiderio S. (2020). Vertebrate sensory ganglia: common and divergent features of the transcriptional programs generating their functional specialization. Front. Cell. Dev. Biol. 8, 587699. 10.3389/fcell.2020.587699 PubMed DOI PMC

Voigt P., Tee W. W., Reinberg D. (2013). A double take on bivalent promoters. Genes. Dev. 27 (12), 1318–1338. 10.1101/gad.219626.113 PubMed DOI PMC

Wang L. L., Serrano C., Zhong X., Ma S., Zou Y., Zhang C. L. (2021a). Revisiting astrocyte to neuron conversion with lineage tracing in vivo . Cell. 184 (21), 5465–5481 e16. 10.1016/j.cell.2021.09.005 PubMed DOI PMC

Wang L.-L., Zhang C.-Li. (2022). In vivo glia‐to‐neuron conversion: pitfalls and solutions. Dev. Neurobiol. 82 (5), 367–374. 10.1002/dneu.22880 PubMed DOI PMC

Wang X., Pei Z., Hossain A., Bai Y., Chen G. (2021b). Transcription factor-based gene therapy to treat glioblastoma through direct neuronal conversion. Cancer Biol. Med. 18 (3), 860–874. 10.20892/j.issn.2095-3941.2020.0499 PubMed DOI PMC

Wapinski O. L., Vierbuchen T., Qu K., Lee Q. Y., Chanda S., Fuentes D. R., et al. (2013). Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell. 155 (3), 621–635. 10.1016/j.cell.2013.09.028 PubMed DOI PMC

Xu D., Zhong L. T., Cheng H. Y., Wang Z. Q., Chen X. M., Feng A. Y., et al. (2023). Overexpressing NeuroD1 reprograms Muller cells into various types of retinal neurons. Neural Regen. Res. 18 (5), 1124–1131. 10.4103/1673-5374.355818 PubMed DOI PMC

Yang X., Lay F., Han H., Jones P. A. (2010). Targeting DNA methylation for epigenetic therapy. Trends Pharmacol. Sci. 31 (11), 536–546. 10.1016/j.tips.2010.08.001 PubMed DOI PMC

Yatoh S., Akashi T., Chan P. P., Kaneto H., Sharma A., Bonner-Weir S., et al. (2007). NeuroD and reaggregation induce beta-cell specific gene expression in cultured hepatocytes. Diabetes/Metabolism Res. Rev. 23 (3), 239–249. 10.1002/dmrr.678 PubMed DOI

Zhang S., Moy W., Zhang H., Leites C., McGowan H., Shi J., et al. (2018). Open chromatin dynamics reveals stage-specific transcriptional networks in hiPSC-based neurodevelopmental model. Stem Cell. Res. 29, 88–98. 10.1016/j.scr.2018.03.014 PubMed DOI PMC

Zhang T., Saunee N. A., Breslin M. B., Song K., Lan M. S. (2012). Functional role of an islet transcription factor, INSM1/IA-1, on pancreatic acinar cell trans-differentiation. J. Cell. Physiol. 227 (6), 2470–2479. 10.1002/jcp.22982 PubMed DOI PMC

Zhang T., Wang H., Saunee N. A., Breslin M. B., Lan M. S. (2010). Insulinoma-associated antigen-1 zinc-finger transcription factor promotes pancreatic duct cell trans-differentiation. Endocrinology 151 (5), 2030–2039. 10.1210/en.2009-1224 PubMed DOI PMC

Zhao M., Amiel S. A., Ajami S., Jiang J., Mohamed R., Heaton N., et al. (2008). Amelioration of streptozotocin-induced diabetes in mice with cells derived from human marrow stromal cells. PLoS ONE 3 (7), e2666. 10.1371/journal.pone.0002666 PubMed DOI PMC