Reprogramming cell fates: reconciling rarity with robustness

被引:216
作者
Huang, Sui [1 ,2 ]
机构
[1] Univ Calgary, Inst Biocomplex & Informat, Calgary, AB, Canada
[2] Harvard Univ, Childrens Hosp, Sch Med, Vasc Biol Program, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
attractor; dynamics; gene regulatory networks; pluripotency; stem cell; PLURIPOTENT STEM-CELLS; LINEAGE-COMMITMENT; GENE-EXPRESSION; TRANSCRIPTION FACTORS; PROGENITOR CELLS; DNA METHYLATION; MOUSE; DIFFERENTIATION; ADULT; PLASTICITY;
D O I
10.1002/bies.200800189
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The stunning possibility of "reprogramming" differentiated somatic cells to express a pluripotent stem cell phenotype (iPS, induced pluripotent stem cell) and the "ground state" character of pluripotency reveal fundamental features of cell fate regulation that lie beyond existing paradigms. The rarity of reprogramming events appears to contradict the robustness with which the unfathomably complex phenotype of stem cells can reliably be generated. This apparent paradox, however, is naturally explained by the rugged "epigenetic landscape" with valleys representing "preprogrammed', attractor states that emerge from the dynamical constraints of the gene regulatory network. This article provides a pedagogical primer to the fundamental principles of gene regulatory networks as integrated dynamic systems and reviews recent insights in gene expression noise and fate determination, thereby offering a formal framework that may help us to understand why cell fate reprogramming events are inherently rare and yet so robust.
引用
收藏
页码:546 / 560
页数:15
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