Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency
Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency
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DOI：
10.1002/stem.1091
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发表时间：
2012-06-01
期刊：
影响因子：
5.2
通讯作者：
Akamatsu, Wado
中科院分区：
文献类型：
--
作者：
Matsui, Takeshi;Takano, Morito;Akamatsu, Wado
使用四种重编程因子（Oct 4、Sox 2、Klf 4和cMyc）从小鼠成纤维细胞直接诱导神经干细胞（NSC），而不克隆分离诱导的多能干细胞（iPSC）。这些NSC甚至在早期传代时产生神经元和神经胶质细胞，而源自克隆胚胎干细胞（ESC）/iPSC的早期NSC主要分化成神经元。表皮生长因子依赖的神经球培养有效地繁殖这些胶质源性神经干细胞，并消除残留的多能细胞，可以形成畸胎瘤在体内。我们的结论是，这些直接诱导的神经干细胞来源于部分重编程的细胞，因为解离的ESC/iPSC在这种培养条件下不形成神经球。这些神经干细胞移植到小鼠纹状体后，在体内分化为神经元和胶质细胞。神经干细胞也可以直接诱导成人成纤维细胞。部分重编程细胞的直接分化可能有助于快速制备具有强烈降低的肿瘤发生倾向的NSC。干细胞2012;30：11091119
Neural stem cells (NSCs) were directly induced from mouse fibroblasts using four reprogramming factors (Oct4, Sox2, Klf4, and cMyc) without the clonal isolation of induced pluripotent stem cells (iPSCs). These NSCs gave rise to both neurons and glial cells even at early passages, while early NSCs derived from clonal embryonic stem cells (ESCs)/iPSCs differentiated mainly into neurons. Epidermal growth factor-dependent neurosphere cultivation efficiently propagated these gliogenic NSCs and eliminated residual pluripotent cells that could form teratomas in vivo. We concluded that these directly induced NSCs were derived from partially reprogrammed cells, because dissociated ESCs/iPSCs did not form neurospheres in this culture condition. These NSCs differentiated into both neurons and glial cells in vivo after being transplanted intracranially into mouse striatum. NSCs could also be directly induced from adult human fibroblasts. The direct differentiation of partially reprogrammed cells may be useful for rapidly preparing NSCs with a strongly reduced propensity for tumorigenesis. STEM CELLS2012;30:11091119