Chemical conversion of human fibroblasts into functional Schwann cells.
Chemical conversion of human fibroblasts into functional Schwann cells.
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DOI：
10.1016/j.stemcr.2014.07.014
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发表时间：
2014-10-14
影响因子：
5.9
通讯作者：
Iacone, Roberto
中科院分区：
文献类型：
--
作者：
Thoma, Eva C.;Merkl, Claudia;Heckel, Tobias;Haab, Rachel;Knoflach, Frederic;Nowaczyk, Corinne;Flint, Nicholas;Jagasia, Ravi;Zoffmann, Sannah Jensen;Truong, Hoa Hue;Petitjean, Pascal;Jessberger, Sebastian;Graf, Martin;Iacone, Roberto
体细胞的直接转分化是获得患者特异性细胞用于多种应用的一种有前景的方法。然而，跨越胚层边界的转换通常需要异位基因表达，从而产生不可预测的副作用。在这里，我们提出了一种无基因方法，允许人类成纤维细胞通过短暂的祖细胞阶段有效转化为施万细胞（周围神经的主要胶质细胞类型）。使用多激酶抑制剂，我们将成纤维细胞转分化为瞬时神经前体细胞，随后进一步分化为雪旺细胞。由此产生的诱导施万细胞 (iSC) 表达大量施万细胞特异性蛋白，并在体外表现出神经支持和髓鞘形成能力。因此，我们建立了一种策略，在化学限定的条件下从人出生后成纤维细胞中获得成熟的雪旺细胞，而不引入异位基因。将人成纤维细胞直接转化为雪旺细胞 不引入异位基因 通过多激酶抑制剂诱导转化 Thoma 及其同事开发了一种仅通过化学处理将人成纤维细胞转化为雪旺细胞的策略。使用多激酶抑制剂，成纤维细胞转分化为瞬时神经前体细胞，并分化为具有雪旺细胞分子和功能特征的细胞。这项研究表明，细胞转化可以仅通过小分子来实现，并提出了一种无需基因修饰即可产生人类雪旺细胞的方法。
Direct transdifferentiation of somatic cells is a promising approach to obtain patient-specific cells for numerous applications. However, conversion across germ-layer borders often requires ectopic gene expression with unpredictable side effects. Here, we present a gene-free approach that allows efficient conversion of human fibroblasts via a transient progenitor stage into Schwann cells, the major glial cell type of peripheral nerves. Using a multikinase inhibitor, we transdifferentiated fibroblasts into transient neural precursors that were subsequently further differentiated into Schwann cells. The resulting induced Schwann cells (iSCs) expressed numerous Schwann cell-specific proteins and displayed neurosupportive and myelination capacity in vitro. Thus, we established a strategy to obtain mature Schwann cells from human postnatal fibroblasts under chemically defined conditions without the introduction of ectopic genes. Direct conversion of human fibroblasts into Schwann cells No introduction of ectopic genes Induction of conversion by multikinase inhibitor Here, Thoma and colleagues developed a strategy to convert human fibroblasts into Schwann cells solely by chemical treatment. Using a multikinase inhibitor, fibroblasts are transdifferentiated into transient neural precursors differentiating into cells with molecular and functional characteristics of Schwann cells. This study shows that cellular conversion can be achieved solely by small molecules and presents an approach to generate human Schwann cells without genetic modifications.
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影响因子：
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