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

Maria Eleni Kastriti, Louis Faure, Dorothea von Ahsen, Thibault Gerald Bouderlique, Johan Bostrom, Tatiana Solovieva, Cameron Jackson, Marianne Bronner, Dies Meijer, Saida Hadjab, Francois Lallemend, Alek Erickson, Marketa Kaucka, Viacheslav Dyachuk, Thomas Perlmann, Laura Lahti, Jan Krivanek, Jean-Francois Brunet, Kaj Fried, Igor Adameyko

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article numbere108780
Number of pages28
JournalEMBO Journal
Early online date11 Jul 2022
Publication statusE-pub ahead of print - 11 Jul 2022

Keywords / Materials (for Non-textual outputs)

  • multipotency
  • neural crest
  • regulons
  • Schwann cell precursors
  • Schwann cell lineage


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