GSE201257
Schwann cell precursors represent a neural crest-like hub state with biased multipotency
Schwann cell precursors (SCPs) are nerve-associated progenitors that not only 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 the atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest have similar transcriptional profiles characterized 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 cell and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knock-out of the 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 toward distinct lineages. Overall design: Smart-Seq2 protocol was performed on single isolated cells by Eukaryotic Single Cell Genomics Facility at SciLifeLab, Stockholm. Single TOMATO+ cells were sorted into 384-well plates prefilled with lysis buffer according to the previously published SmartSeq2 protocol (Picelli, Faridani et al. 2014) using a BD FACSAria Fusion Cell Sorter B5/R3/V3 system with a three-laser configuration (488nm, 633nm, and 405nm) and 16 fluorescence detectors. Single-cell transcriptomic sequencing was performed as previously described (Picelli, Faridani et al. 2014).