Reprogramming progressive cells display low CAG promoter activity. (4th November 2020)

• Record Type: Journal Article
• Authors: Hu, Xiao; Wu, Qiao; Zhang, Jian; Kim, Jonghun; Chen, Xinyue; Hartman, Amaleah A.; Eastman, Anna E.; Park, In-Hyun; Guo, Shangqin
• Is Part Of: Stem cells. Volume 39:Number 1(2021)
• Page Start: 43
• Page End: 54
• Publication Date: 2020-11-04
• Subjects: CAG promoter -- cell cycle speed -- cell size -- MKL1/SRF signaling -- Yamanaka reprogramming; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3295
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: 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 low 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. Abstract : 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. CAG low cells are small in size, cycle fast and display low endogenous MKL1/SRF activity.