Department of Cell Biology, Yale University, New Haven, Connecticut, USA.
Yale Stem Cell Center, Yale University, New Haven, Connecticut, USA.
Stem Cells. 2021 Jan;39(1):43-54. doi: 10.1002/stem.3295. Epub 2020 Nov 4.
There is wide variability in the propensity of somatic cells to reprogram into pluripotency in response to the Yamanaka factors. How to segregate these variabilities to enrich for cells of specific traits that reprogram efficiently remains challenging. Here we report that the variability in reprogramming propensity is associated with the activity of the MKL1/SRF transcription factor and concurs with small cell size as well as rapid cell cycle. Reprogramming progressive cells can be prospectively identified by their low activity of a widely used synthetic promoter, CAG. CAG cells arise and expand during cell cycle acceleration in the early reprogramming culture of both mouse and human fibroblasts. Our work illustrates a molecular scenario underlying the distinct reprogramming propensities and demonstrates a convenient practical approach for their enrichment.
体细胞对山中因子重编程为多能性的能力存在广泛的可变性。如何将这些可变性分离出来，以富集高效重编程的特定特征细胞仍然具有挑战性。在这里，我们报告说，重编程倾向的可变性与 MKL1/SRF 转录因子的活性有关，并与小细胞大小以及快速细胞周期相一致。通过其广泛使用的合成启动子 CAG 的低活性，可以前瞻性地识别重编程渐进细胞。CAG 细胞在小鼠和人成纤维细胞的早期重编程培养过程中细胞周期加速时出现并扩增。我们的工作说明了不同重编程倾向的分子情况，并展示了一种方便实用的富集方法。
