Reprogramming progressive cells display low CAG promoter activity.
Reprogramming progressive cells display low CAG promoter activity.
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DOI：
10.1002/stem.3295
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Guo S
中科院分区：
文献类型：
--
作者：
Hu X;Wu Q;Zhang J;Kim J;Chen X;Hartman AA;Eastman AE;Park IH;Guo S
体细胞响应山中因子而重编程为多能性的倾向存在很大差异。如何分离这些变异性以富集具有特定性状的细胞，从而有效地重新编程仍然具有挑战性。在这里，我们报告重编程倾向的变异性与 MKL1/SRF 转录因子的活性相关，并且与小细胞尺寸和快速细胞周期一致。重编程进行性细胞可以通过广泛使用的合成启动子 CAG 的低活性进行前瞻性鉴定。在小鼠和人类成纤维细胞的早期重编程培养物中，CAGlow 细胞在细胞周期加速过程中产生并扩增。我们的工作阐明了不同重编程倾向背后的分子场景，并展示了一种方便实用的富集方法。进行山中重编程的培养物中存在广泛的细胞异质性。识别重编程进行性细胞的能力具有实际和机制意义。我们报告说，重编程进行性细胞可以通过广泛使用的合成启动子（CAG 启动子）的低活性来方便地识别。 CAGlow 细胞体积小、循环快且内源性 MKL1/SRF 活性低。
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. CAGlow 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. Extensive cellular heterogeneity exists in cultures undergoing Yamanaka reprogramming. The ability to identify reprogramming progressive cells has practical and mechanistic implications. We report that reprogramming progressive cells can be conveniently identified by the low activity of a widely used synthetic promoter, the CAG promoter. CAGlow cells are small in size, cycle fast and display low endogenous MKL1/SRF activity.
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