Repressor Element 1 Silencing Transcription Factor Couples Loss of Pluripotency with Neural Induction and Neural Differentiation
Repressor Element 1 Silencing Transcription Factor Couples Loss of Pluripotency with Neural Induction and Neural Differentiation
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DOI：
10.1002/stem.1004
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发表时间：
2012-03-01
期刊：
影响因子：
5.2
通讯作者：
Buckley, Noel J.
中科院分区：
文献类型：
--
作者：
Soldati, Chiara;Bithell, Angela;Buckley, Noel J.
胚胎干细胞的神经分化需要多能性调控程序的协同抑制和神经源性调控程序的相互激活。在神经诱导后，ESC快速抑制多能性基因的表达，随后分阶段激活神经祖细胞和分化的神经元和神经胶质基因。维持多能性的转录因子的部分特点，而那些潜在的神经诱导少得多的探索，协调这两个发展计划的因素是完全未知的。一种转录因子REST（阻遏元件1沉默转录因子）已与神经祖细胞的终末分化有关，最近也有争议地与多能性的控制有关。在这里，我们表明，在没有REST的情况下，多能性和神经诱导的协调丢失，并且多能性基因的抑制和神经祖细胞和分化的神经元和神经胶质基因的过早激活会延迟。此外，我们表明，REST是不需要的放射状胶质样祖细胞的生产，但需要其随后的维护和分化为神经元，少突胶质细胞和星形胶质细胞。我们认为，REST作为一个调节中心，协调及时镇压多能性与神经诱导和神经分化。干细胞2012;30：425-434
Neural differentiation of embryonic stem cells (ESCs) requires coordinated repression of the pluripotency regulatory program and reciprocal activation of the neurogenic regulatory program. Upon neural induction, ESCs rapidly repress expression of pluripotency genes followed by staged activation of neural progenitor and differentiated neuronal and glial genes. The transcriptional factors that underlie maintenance of pluripotency are partially characterized whereas those underlying neural induction are much less explored, and the factors that coordinate these two developmental programs are completely unknown. One transcription factor, REST (repressor element 1 silencing transcription factor), has been linked with terminal differentiation of neural progenitors and more recently, and controversially, with control of pluripotency. Here, we show that in the absence of REST, coordination of pluripotency and neural induction is lost and there is a resultant delay in repression of pluripotency genes and a precocious activation of both neural progenitor and differentiated neuronal and glial genes. Furthermore, we show that REST is not required for production of radial glia-like progenitors but is required for their subsequent maintenance and differentiation into neurons, oligodendrocytes, and astrocytes. We propose that REST acts as a regulatory hub that coordinates timely repression of pluripotency with neural induction and neural differentiation. STEM CELLS 2012;30:425-434