REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells.
REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells.
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DOI：
10.1371/journal.pone.0145280
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Pyle AD
中科院分区：
文献类型：
--
作者：
Thakore-Shah K;Koleilat T;Jan M;John A;Pyle AD
REST（RE 1 silencing transcription factor，RE 1沉默转录因子），又称NRSF（neuron-restrictive silencer factor，神经元限制性沉默因子），是一种已知的非神经组织和干细胞中神经基因的转录抑制因子。REST活性的失调被认为在包括癫痫、癌症、唐氏综合征和亨廷顿病在内的多种疾病中起作用。REST/NRSF在控制人胚胎干细胞（hESC）命运中的作用从未被研究过。为了评估REST在hESC中的作用，我们开发了一种诱导型REST敲低系统，并在短期和长期培养中检查了生长和分化。有趣的是，我们发现改变多个hESC系中的REST水平不会导致自我更新的丧失，而是会导致生存率的提高。在分化过程中，REST敲低导致MAPK/ERK和WNT信号传导增加，中内胚层分化标志物表达增加。因此，我们发现了REST在调节人类胚胎干细胞生长和早期分化决策中的新作用。
REST (RE1 silencing transcription factor), also known as NRSF (neuron-restrictive silencer factor), is a well-known transcriptional repressor of neural genes in non-neural tissues and stem cells. Dysregulation of REST activity is thought to play a role in diverse diseases including epilepsy, cancer, Down’s syndrome and Huntington’s disease. The role of REST/NRSF in control of human embryonic stem cell (hESC) fate has never been examined. To evaluate the role of REST in hESCs we developed an inducible REST knockdown system and examined both growth and differentiation over short and long term culture. Interestingly, we have found that altering REST levels in multiple hESC lines does not result in loss of self-renewal but instead leads to increased survival. During differentiation, REST knockdown resulted in increased MAPK/ERK and WNT signaling and increased expression of mesendoderm differentiation markers. Therefore we have uncovered a new role for REST in regulation of growth and early differentiation decisions in human embryonic stem cells.