Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
Department of Biostatistics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA.
Mol Syst Biol. 2018 Sep 3;14(9):e8140. doi: 10.15252/msb.20178140.
It is well known that clonal cells can make different fate decisions, but it is unclear whether these decisions are determined during, or before, a cell's own lifetime. Here, we engineered an endogenous fluorescent reporter for the pluripotency factor OCT4 to study the timing of differentiation decisions in human embryonic stem cells. By tracking single-cell OCT4 levels over multiple cell cycle generations, we found that the decision to differentiate is largely determined before the differentiation stimulus is presented and can be predicted by a cell's preexisting OCT4 signaling patterns. We further quantified how maternal OCT4 levels were transmitted to, and distributed between, daughter cells. As mother cells underwent division, newly established OCT4 levels in daughter cells rapidly became more predictive of final OCT4 expression status. These results imply that the choice between developmental cell fates can be largely predetermined at the time of cell birth through inheritance of a pluripotency factor.
众所周知，克隆细胞可以做出不同的命运决定，但尚不清楚这些决定是在细胞自身寿命期间还是之前做出的。在这里，我们设计了一种内源性荧光报告基因来研究多能性因子 OCT4 在人类胚胎干细胞中的分化决定的时间。通过在多个细胞周期世代中跟踪单细胞 OCT4 水平，我们发现分化的决定主要是在分化刺激出现之前做出的，并且可以通过细胞预先存在的 OCT4 信号模式来预测。我们进一步量化了母细胞 OCT4 水平如何传递到子细胞之间并在子细胞之间分配。随着母细胞的分裂，新建立的子细胞中的 OCT4 水平迅速变得更能预测最终的 OCT4 表达状态。这些结果表明，通过多能性因子的遗传，细胞出生时就可以在很大程度上预先确定发育细胞命运之间的选择。
