Direct genesis of functional rodent and human schwann cells from skin mesenchymal precursors.

Direct genesis of functional rodent and human schwann cells from skin mesenchymal precursors.
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DOI:
10.1016/j.stemcr.2014.05.011
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发表时间:
2014-07-08
期刊:
影响因子:
5.9
通讯作者:
Miller, Freda D.
Miller, Freda D.
中科院分区:
医学1区
文献类型:
--
作者:
Krause, Matthew P.;Dworski, Shaalee;Feinberg, Konstantin;Jones, Karen;Johnston, Adam P. W.;Paul, Smitha;Paris, Maryline;Peles, Elior;Bagli, Darius;Forrest, Christopher R.;Kaplan, David R.;Miller, Freda D.

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最近关于定向重编程的报道提出了关于细胞谱系稳定性的问题。在这里,我们已经解决了这个问题,专注于皮肤来源的前体细胞(SKPs),一种真皮来源的前体细胞。我们通过谱系追踪表明,来自背部皮肤的小鼠SKPs起源于间充质细胞,而不是神经嵴来源的细胞。这些间充质来源的SKPs可以在没有遗传操作的情况下产生功能性雪旺细胞,一种神经嵴细胞类型,并且在转录水平上与从外周神经分离的雪旺细胞高度相似。这不是小鼠特异性现象,因为在转录组水平高度相似的人SKPs可以由神经嵴衍生的面部和中胚层衍生的包皮真皮制成,并且包皮SKPs可以产生髓鞘形成的施旺细胞。因此,非神经嵴衍生的间充质前体细胞可以分化成真正的周围神经胶质细胞在没有遗传操作,这表明发育定义的谱系边界比广泛认为的更灵活。啮齿动物真皮间充质前体分化成功能性雪旺细胞间充质雪旺细胞与神经嵴雪旺细胞高度相似SKPs可以由人神经嵴和中胚层真皮制成人中胚层包皮SKPs分化成功能性雪旺细胞在这里,米勒和同事表明,来自背部皮肤的鼠SKPs起源于间充质细胞,但它们仍然产生真正的雪旺细胞,神经嵴细胞类型。这不是小鼠特异性的,因为中胚层来源的人SKPs也产生功能性雪旺细胞。因此,间充质前体产生周围神经胶质细胞没有遗传操作,这表明发育定义的谱系边界比广泛认为的更灵活。
Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs), a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought. Rodent dermal mesenchymal precursors differentiate into functional Schwann cells Mesenchymal Schwann cells are highly similar to neural crest Schwann cells SKPs can be made from human neural crest and mesodermal dermis Human mesodermal foreskin SKPs differentiate into functional Schwann cells Here, Miller and colleagues show that murine SKPs from dorsal skin originate from mesenchymal cells but that they nonetheless generate bona fide Schwann cells, a neural crest cell type. This is not mouse specific, since mesodermally derived human SKPs also make functional Schwann cells. Thus, mesenchymal precursors generate peripheral glia without genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than is widely thought.
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