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

First Author  Kastriti ME Year  2022
Journal  EMBO J Volume  41
Issue  17 Pages  e108780
PubMed ID  35815410 Mgi Jnum  J:328996
Mgi Id  MGI:7341314 Doi  10.15252/embj.2021108780
Citation  Kastriti ME, et al. (2022) Schwann cell precursors represent a neural crest-like state with biased multipotency. EMBO J 41(17):e108780
abstractText  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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