Schwann cell precursors represent a neural crest-like state with biased multipotency.
Schwann cell precursors represent a neural crest-like state with biased multipotency.
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DOI：
10.15252/embj.2021108780
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发表时间：
2022-09-01
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雪旺细胞前体（SCPs）是神经相关的祖细胞，可以产生髓鞘化和非髓鞘化的雪旺细胞，但也像它们起源的神经嵴细胞一样具有多能性。在脊椎动物胚胎的整个身体中，scp普遍存在于生长的周围神经中。通过使用单细胞转录组学来生成整个神经嵴谱系的基因表达图谱，我们发现早期scp和晚期迁移嵴细胞具有相似的转录谱，其特征是多能的“枢纽”状态，其中包含偏向传统神经嵴命运的细胞。scp在被诱导为终末雪旺细胞和其他细胞后，继续从神经嵴分化，不同的亚型存在于不同的解剖位置。利用CRISPR - Cas9功能缺失进行的功能实验进一步表明，敲除常见的“中枢”基因Sox8，通过促进scp向交感肾上腺细胞分化，导致沿周围神经的神经嵴来源细胞出现缺陷。最后，在黑色素瘤、神经纤维瘤和神经母细胞瘤中发现的特定肿瘤群体与SCP/雪旺细胞发育的不同阶段相对应。总的来说，scp类似于迁移的神经嵴细胞，它们保持多能性，并被转录为不同的谱系。一项转录、时间和空间的单细胞分析资源揭示了雪旺细胞祖细胞是发育中的小鼠胚胎中神经嵴样细胞的多能来源。
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. A transcriptional, temporal and spatial single‐cell profiling resource uncovers Schwann cell progenitors as a multipotent source of neural crest‐like cells in the developing mouse embryo.
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影响因子：
64.5
作者：
Adameyko, Igor;Lallemend, Francois;Ernfors, Patrik
通讯作者：
Ernfors, Patrik
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作者：
CHONG, JHA;TAPIARAMIREZ, J;MANDEL, G
通讯作者：
MANDEL, G
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通讯作者：
Kharchenko, Peter V.
影响因子：
4.8
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通讯作者：
Schuurmans C
影响因子：
64.8
作者：
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