英国剑桥大学José C.R. Silva研究团队发现了不同的分子轨迹会聚，诱导细胞原始多能性。相关论文发表在2019年9月出版的《细胞—干细胞》上。

研究通过转录和机制上不同的途径，获得原始多能性干细胞。从植入外胚层干细胞（EpiSCs）开始，一种途径在原始多能性诱导之前进入中胚层状态，而另一种途径短暂地模拟早期内部细胞团，并相应地获得更大的发育潜力。这些途径利用不同的信号传导网络和转录因子，但随后汇聚于相同的原始终点，在身份转变的潜在机制中显示出令人惊讶的灵活性，并表明原始多能性是能被多种因素诱导的状态。通过精确表达Oct4作为一个统一的、主要的和充分的特征，来协调这些途径差异。研究表明，这种“转换因子”的微调调控提供了多维获取原始多能性的途径，为理解细胞身份转换提供了一个概念框架。

研究人员表示，了解细胞身份转变是如何发生的，以及相同的起始状态和结束状态之间是否存在多条路径，是被广泛关注的问题。

附：英文原文

Title: Distinct Molecular Trajectories Converge to Induce Naive Pluripotency

Author: Hannah T. Stuart, Giuliano G. Stirparo, Tim Lohoff, Lawrence E. Bates, Masaki Kinoshita, Chee Y. Lim, Elsa J. Sousa, Katsiaryna Maskalenka, Aliaksandra Radzisheuskaya, Andrew A. Malcolm, Mariana R.P. Alves, Rebecca L. Lloyd, Sonia Nestorowa, Peter Humphreys, William Mansfield, Wolf Reik, Paul Bertone, Jennifer Nichols, Berthold Gttgens, José C.R. Silva

Issue&Volume: Volume 25 Issue 3

Abstract: Understanding how cell identity transitions occur and whether there are multiple paths between the same beginning and end states are questions of wide interest. Here we show that acquisition of naive pluripotency can follow transcriptionally and mechanistically distinct routes. Starting from post-implantation epiblast stem cells (EpiSCs), one route advances through a mesodermal state prior to naive pluripotency induction, whereas another transiently resembles the early inner cell mass and correspondingly gains greater developmental potency. These routes utilize distinct signaling networks and transcription factors but subsequently converge on the same naive endpoint, showing surprising flexibility in mechanisms underlying identity transitions and suggesting that naive pluripotency is a multidimensional attractor state. These route differences are reconciled by precise expression of Oct4 as a unifying, essential, and sufficient feature. We propose that fine-tuned regulation of this "transition factor" underpins multidimensional access to naive pluripotency, offering a conceptual framework for understanding cell identity transitions.

DOI: 10.1016/j.stem.2019.07.009

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30307-8