REST/NRSF基因敲低改变人类胚胎干细胞的存活、谱系分化和信号传导
REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells.
作者信息
Thakore-Shah Kaushali, Koleilat Tasneem, Jan Majib, John Alan, Pyle April D
机构信息
Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095, United States of America.
California State University, Northridge, CA, 91325, United States of America.
出版信息
PLoS One. 2015 Dec 21;10(12):e0145280. doi: 10.1371/journal.pone.0145280. eCollection 2015.
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.
REST（RE1沉默转录因子），也被称为NRSF（神经元限制性沉默因子），是一种在非神经组织和干细胞中广为人知的神经基因转录抑制因子。REST活性失调被认为在多种疾病中起作用，包括癫痫、癌症、唐氏综合征和亨廷顿舞蹈症。REST/NRSF在控制人类胚胎干细胞（hESC）命运中的作用从未被研究过。为了评估REST在hESC中的作用，我们开发了一种可诱导的REST敲低系统，并在短期和长期培养中研究了其生长和分化情况。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能力丧失，反而会提高细胞存活率。在分化过程中，REST敲低导致MAPK/ERK和WNT信号增强以及中胚层分化标志物的表达增加。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定中的新作用。
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