Dedifferentiation of foetal CNS stem cells to mesendoderm-like cells through an EMT process.
Dedifferentiation of foetal CNS stem cells to mesendoderm-like cells through an EMT process.
复制标题
DOI：
10.1371/journal.pone.0030759
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Surani MA
中科院分区：
文献类型：
--
作者：
Ber S;Lee C;Voiculescu O;Surani MA
组织特异性干细胞被认为具有有限的分化潜能。最近，这一概念受到了挑战的报告，显示了更广泛的分化潜力的神经干细胞，在体外和体内，虽然调节神经干细胞的可塑性的分子机制是未知的。在这里，我们报告了来自小鼠胚胎皮层的神经干细胞在体外响应于Lif和血清，并在48小时内经历上皮向间充质转化（EMT）介导的去分化过程，以及多能性标志物的瞬时上调，更值得注意的是，中内胚层基因Brachyury（T）和Sox 17的上调。将这些诱导的推定中内胚层细胞注射到早期原肠胚中，这表明与未诱导的细胞相比，它们更有效地整合到中胚层和内胚层谱系中。我们还发现，TGFβ和Jak/Stat途径是必要的，但不足以诱导神经干细胞中的中内胚层表型。这些结果为研究EMT对神经干细胞可塑性的调控提供了新的思路。剖析参与这些过程的调控途径可能有助于控制细胞命运的决定。
Tissue-specific stem cells are considered to have a limited differentiation potential. Recently, this notion was challenged by reports that showed a broader differentiation potential of neural stem cells, in vitro and in vivo, although the molecular mechanisms that regulate plasticity of neural stem cells are unknown. Here, we report that neural stem cells derived from mouse embryonic cortex respond to Lif and serum in vitro and undergo epithelial to mesenchymal transition (EMT)-mediated dedifferentiation process within 48 h, together with transient upregulation of pluripotency markers and, more notably, upregulation of mesendoderm genes, Brachyury (T) and Sox17. These induced putative mesendoderm cells were injected into early gastrulating chick embryos, which revealed that they integrated more efficiently into mesoderm and endoderm lineages compared to non-induced cells. We also found that TGFβ and Jak/Stat pathways are necessary but not sufficient for the induction of mesendodermal phenotype in neural stem cells. These results provide insights into the regulation of plasticity of neural stem cells through EMT. Dissecting the regulatory pathways involved in these processes may help to gain control over cell fate decisions.
登录
查看更多内容
影响因子：
5.2
作者：
Direkze, NC;Forbes, SJ;Wright, NA
通讯作者：
Wright, NA
影响因子：
50.3
作者：
Ansieau, Stephane;Bastid, Jeremy;Puisieux, Alain
通讯作者：
Puisieux, Alain
影响因子：
3.3
作者：
Arnoux, Valerie;Nassour, Mayssaa;Savagner, Pierre
通讯作者：
Savagner, Pierre
影响因子：
4
作者：
Bolós, V;Peinado, H;Cano, A
通讯作者：
Cano, A
影响因子：
3.7
作者：
Holmberg J;He X;Peredo I;Orrego A;Hesselager G;Ericsson C;Hovatta O;Oba-Shinjo SM;Marie SK;Nistér M;Muhr J
通讯作者：
Muhr J