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Scalable generation of Schwann cell precursors from human pluripotent stem cells

ABSTRACT: Schwann cells (SCs) are an absolute prerequisite for development of effective treatment of myelin disorders and nerve injuries. However, human sources of functional, myelinating SCs are extremely limited. Here, we have developed a novel, efficient strategy for producing directly an unlimited supply of functional human SCs via successful derivation of expandable Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs) (hPSC-SCPs). Functional and molecular characteristics of SCs from hPSC-SCPs (hPSC-SCP-SCs) appeared to be similar to those of authentic Schwann cells. As a novel therapeutic target, transplanted hPSC-SCP-SCs effectively promoted axonal regeneration through directly myelinating regenerated-axons in sciatic nerve injured mice. Here, we present hPSC-SCPs and hPSC-SCP-SCs as an outstanding resource to use for investigating human Schwann cell pathology and biology and for translational approaches to PNS and CNS repair and regeneration.

ORGANISM(S): Homo sapiens

PROVIDER: GSE95004 | GEO | 2017/08/15

SECONDARY ACCESSION(S): PRJNA375112

REPOSITORIES: GEO

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

Project description: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.

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The molecular profile and ability to promote axon regeneration after peripheral nerve injury by Repair Schwann cells is distinctly different from that for developing Schwann cells

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Matrix metalloproteinase-9 and TIMP-1 in peripheral nerve: Implications for myelin formation

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IL-22 impedes the proliferation of Schwann cells and influence nerve regeneration

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hESC- and hiPSC-derived Schwann cells are Molecularly and Functionally Equivalent

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Nerve-derived Schwann cell precursors, acting in a paracrine fashion, are essential for mammalian digit tip regeneration [MOUSE]

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