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Schwann cell precursors represent a neural crest-like state with biased multipotency

ME. Kastriti, L. Faure, D. Von Ahsen, TG. Bouderlique, J. Boström, T. Solovieva, C. Jackson, M. Bronner, D. Meijer, S. Hadjab, F. Lallemend, A. Erickson, M. Kaucka, V. Dyachuk, T. Perlmann, L. Lahti, J. Krivanek, JF. Brunet, K. Fried, I. Adameyko

. 2022 ; 41 (17) : e108780. [pub] 20220711

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024553

Grantová podpora
R01 DE027568 NIDCR NIH HHS - United States

Schwann cell precursors (SCPs) are nerve-associated progenitors that can generate myelinating and non-myelinating Schwann cells but also are multipotent like the neural crest cells from which they originate. SCPs are omnipresent along outgrowing peripheral nerves throughout the body of vertebrate embryos. By using single-cell transcriptomics to generate a gene expression atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest cells have similar transcriptional profiles characterised by a multipotent "hub" state containing cells biased towards traditional neural crest fates. SCPs keep diverging from the neural crest after being primed towards terminal Schwann cells and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knockout of the common "hub" gene Sox8 causes defects in neural crest-derived cells along peripheral nerves by facilitating differentiation of SCPs towards sympathoadrenal fates. Finally, specific tumour populations found in melanoma, neurofibroma and neuroblastoma map to different stages of SCP/Schwann cell development. Overall, SCPs resemble migrating neural crest cells that maintain multipotency and become transcriptionally primed towards distinct lineages.

Citace poskytuje Crossref.org

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$a Kastriti, Maria Eleni $u Department of Molecular Neuroscience, Center for Brain Research, Medical University Vienna, Vienna, Austria $u Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden $u Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria $1 https://orcid.org/0000000205637399
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$a Schwann cell precursors (SCPs) are nerve-associated progenitors that can generate myelinating and non-myelinating Schwann cells but also are multipotent like the neural crest cells from which they originate. SCPs are omnipresent along outgrowing peripheral nerves throughout the body of vertebrate embryos. By using single-cell transcriptomics to generate a gene expression atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest cells have similar transcriptional profiles characterised by a multipotent "hub" state containing cells biased towards traditional neural crest fates. SCPs keep diverging from the neural crest after being primed towards terminal Schwann cells and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knockout of the common "hub" gene Sox8 causes defects in neural crest-derived cells along peripheral nerves by facilitating differentiation of SCPs towards sympathoadrenal fates. Finally, specific tumour populations found in melanoma, neurofibroma and neuroblastoma map to different stages of SCP/Schwann cell development. Overall, SCPs resemble migrating neural crest cells that maintain multipotency and become transcriptionally primed towards distinct lineages.
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$a Solovieva, Tatiana $u Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA $1 https://orcid.org/0000000161942550
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$a Jackson, Cameron $u Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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$a Bronner, Marianne $u Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA $1 https://orcid.org/0000000342741862
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$a Meijer, Dies $u Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK $1 https://orcid.org/0000000284616341
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$a Hadjab, Saida $u Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
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$a Lallemend, Francois $u Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
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$a Erickson, Alek $u Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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$a Kaucka, Marketa $u Max Planck Institute for Evolutionary Biology, Plön, Germany $1 https://orcid.org/0000000287819769
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$a Dyachuk, Viacheslav $u Almazov Federal Medical Research Centre, Saint Petersburg, Russia
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$a Perlmann, Thomas $u Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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$a Lahti, Laura $u Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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$a Krivanek, Jan $u Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic $1 https://orcid.org/000000027590187X
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$a Brunet, Jean-Francois $u Institut de Biologie de l'ENS (IBENS), INSERM, CNRS, École Normale Supérieure, PSL Research University, Paris, France
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$a Fried, Kaj $u Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
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$a Adameyko, Igor $u Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden $u Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Vienna, Austria $1 https://orcid.org/0000000154710356
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