包含RE1沉默转录因子和miR-21的胚胎干细胞调控网络的双稳开关及鲁棒性的研究  

The Switch of the Transcriptional Network with REST and miR-21 in Embryonic Stem Cells and Its Robustness Analysis

作　　者：贺勤斌[1,2] 郝军军[1] 蔡水明[1] 王瑞琦[1] 刘曾荣[1] 

机构地区：[1]上海大学系统生物技术研究所,上海200444 [2]台州学院数学系,浙江临海317000

出　　处：《生物物理学报》2011年第12期1054-1064,共11页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(10832006;11172158)

摘　　要：建立了包含RE1沉默转录因子(RE1-silencing transcription factor,REST)和miR-21,以及转录因子OCT4、SOX2和NANOG的胚胎干细胞(ES细胞)核心调控网络的数学模型,证明该调控网络存在双稳开关,并分析了REST和miR-21对双稳开关的影响,发现改变REST或miR-21的浓度,会引起双稳开关曲线的平移及双稳区域长度的变化。同时,还讨论了胚胎干细胞调控网络的两种外部输入信号A和B与双稳开关鲁棒性的关系,结果表明,通过适当地组合两种外部输入信号,能够得到更加鲁棒的双稳开关。我们推测,信号A在维持正常ES细胞的自我更新及分化中起主要作用,信号B则在维持胚胎干细胞调控网络的鲁棒性中起重要作用。In this paper,we present a computational model for the transcriptional network in embryonic stem cells（ESCs） involving the REST（RE1-silencing transcription factor）,miR-21,and the transcription factors OCT4,SOX2 and NANOG.The model suggests that there is a bistable switch in the transcription network and shows that REST and miR-21 play critical roles in dynamics of the switch.Specifically,changing the concentration of REST or miR-21 will lead to the shift of bistable switching curve,as well as the changes in length of bistable region.At the same time,the relationship between two external input signals,A and B,and the robustness of the switch are also discussed.It is shown that a more robust switch can be obtained through appropriate combination of the two external signals.In addition,the model suggests that the main role of external input A is to maintain self-renewal and pluripotency of ESCs.In contrast,the external input B plays a key role in increasing robustness of the switch.

关 键 词：胚胎干细胞 双稳开关 鲁棒性 分化 自我更新 

分 类 号：Q332[生物学—遗传学]