Chen Xinyue, Hartman Amaleah, Guo Shangqin
Department of Cell Biology, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520 USA.
Curr Stem Cell Rep. 2015;1(3):129-138. doi: 10.1007/s40778-015-0018-0. Epub 2015 Jul 1.
A close relationship between proliferation and cell fate specification has been well documented in many developmental systems. In addition to the gradual cell fate changes accompanying normal development and tissue homeostasis, it is now commonly appreciated that cell fate could also undergo drastic changes, as illustrated by the induction of pluripotency from many differentiated somatic cell types during the process of Yamanaka reprogramming. Strikingly, the drastic cell fate change induced by Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) is preceded by extensive cell cycle acceleration. Prompted by our recent discovery that progression toward pluripotency from rare somatic cells could bypass the stochastic phase of reprogramming and that a key feature of these somatic cells is an ultrafast cell cycle (~8 h/cycle), we assess whether cell cycle dynamics could provide a general framework for controlling cell fate. Several potential mechanisms on how cell cycle dynamics may impact cell fate determination by regulating chromatin, key transcription factor concentration, or their interactions are discussed. Specific challenges and implications for studying and manipulating cell fate are considered.
增殖与细胞命运特化之间的密切关系在许多发育系统中都有充分的记录。除了伴随正常发育和组织稳态的细胞命运逐渐变化外，现在人们普遍认识到细胞命运也可能发生剧烈变化，山中重编程过程中从许多分化的体细胞类型诱导多能性就说明了这一点。引人注目的是，山中因子（Oct4、Sox2、Klf4和c-Myc）诱导的剧烈细胞命运变化之前会出现广泛的细胞周期加速。基于我们最近的发现，即从稀有体细胞向多能性的进展可以绕过重编程的随机阶段，并且这些体细胞的一个关键特征是超快细胞周期（约8小时/周期），我们评估细胞周期动力学是否可以为控制细胞命运提供一个通用框架。讨论了细胞周期动力学如何通过调节染色质、关键转录因子浓度或它们的相互作用来影响细胞命运决定的几种潜在机制。考虑了研究和操纵细胞命运的具体挑战和意义。
