郭蒙蒙,应其龙,叶守东.Id2诱导Myc表达促进小鼠胚胎干细胞自我更新[J].生物化学与生物物理进展(待发表)
Id2诱导Myc表达促进小鼠胚胎干细胞自我更新
Id2 promotes mouse embryonic stem cell self-renewal through induction of the expression levels of Myc family members
投稿时间:2017-05-17  修订日期:2017-08-30
中文关键词:  胚胎干细胞,自我更新,Id2,Myc
英文关键词:Embryonic stem cell, Self-renewal, Id2, Myc
基金项目:国家和安徽省自然科学基金(31501191, 31671535, 1508085SQC204)以及安徽大学科研条件建设基金(J01006068,J01006045)资助项目
作者单位E-mail
郭蒙蒙 安徽大学干细胞及转化医学研究中心 1099715311@qq.com 
应其龙 美国南加州大学Keck医学院干细胞与再生医学研究中心,洛杉矶  
叶守东 安徽大学干细胞及转化医学研究中心 shdye@126.com 
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中文摘要:
      小鼠胚胎干细胞 (Mouse embryonic stem cells, mESCs) 分离自小鼠的囊胚内细胞团,在体外具有无限的自我更新能力和多向分化的潜能,因此拥有重大的社会和经济效益.前期人们发现DNA结合抑制因子1 (inhibitor of DNA binding 1,Id1) 在含血清培养条件下,可以促进mESCs自我更新,但其家族成员,如Id2和Id3,在mESCs中的作用尚不清楚. 本课题在mESCs里分别上调Id2和Id3基因的表达,发现它们在含血清的培养条件下均具有促进mESCs自我更新的能力,但Id2促进自我更新的能力大于Id3. 接着通过转录组测序技术发现Id2上调c-Myc和n-Myc基因的表达水平. 最后功能性验证实验证实只有同时干扰c-Myc和n-Myc基因的表达才能够极大地削弱Id2维持mESCs未分化状态的作用,表明Id2主要通过诱导Myc家族成员的表达来促进mESCs的自我更新. 本研究结果将扩大人们对干细胞多能性调控网络的认识,利于干细胞未来的基础研究和安全应用.
英文摘要:
      Mouse embryonic stem cells (mESCs) are isolated from the inner cell mass (ICM) of the pre-implantation embryos. They can be maintained indefinitely as self-renewing populations while retaining the pluripotency to differentiate into the cells of all three primary germ layers when cultured under appropriate conditions in vitro. The transcriptional factor inhibitor of DNA binding 1 (Id1) can promote mESC self-renewal in serum condition without LIF. However, whether the other Id family members, such as Id2 and Id3, have similar function in mESCs is still unclear. In this study, we overexpressed Id2 and Id3 in 46C mESCs respectively, and found that both factors are able to support mESC self-renewal in the absence of LIF, while the self-renewal-promoting effect of Id2 is stronger than Id3. RNA-sequence approach revealed that Id2 is capable of upregulating c-Myc and n-Myc expression levels. Functional studies demonstrated that knockdown of c-Myc and n-Myc together could greatly reduce the function of Id2 in sustaining the undifferentiated state of mESCs, indicating that Myc family members have functional redundancy and can mediate the self-renewal-promoting effect of Id2 in mESCs. Our results will expand the current understanding of the pluripotency regulation network of embryonic stem cells.
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