KLF3 promotes the 8‐cell‐like transcriptional state in pluripotent stem cells

Jing Hao; Xi Yang; Chao Zhang; Xue‐Tao Zhang; Ming Shi; Shao‐Hua Wang; Li Mi; Yu‐Ting Zhao; Huiqing Cao; Yangming Wang

doi:10.1111/cpr.12914

journal article Open Access Sep 29, 2020

KLF3 promotes the 8‐cell‐like transcriptional state in pluripotent stem cells

Jing Hao

Xi Yang

Chao Zhang

Xue‐Tao Zhang Ming Shi

Shao‐Hua Wang Li Mi

Yu‐Ting Zhao Huiqing Cao Yangming Wang

Cell Proliferation Vol. 53 No. 11 · Wiley

View at Publisher Save 10.1111/cpr.12914

Abstract

AbstractObjectivesMouse embryonic stem cell (mESC) culture contains various heterogeneous populations, which serve as excellent models to study gene regulation in early embryo development. The heterogeneity is typically defined by transcriptional activities, for example, the expression of Nanog or Rex1 mRNA. Our objectives were to identify mESC heterogeneity that are caused by mechanisms other than transcriptional control.Materials and methodsKlf3 mRNA and protein were analysed by RT‐qPCR, Western blotting or immunofluorescence in mESCs, C2C12 cells, early mouse embryos and various mouse tissues. An ESC reporter line expressing KLF3‐GFP fusion protein was made to study heterogeneity of KLF3 protein expression in ESCs. GFP‐positive mESCs were sorted for further analysis including RT‐qPCR and RNA‐seq.ResultsIn the majority of mESCs, KLF3 protein is actively degraded due to its proline‐rich sequence and highly disordered structure. Interestingly, KLF3 protein is stabilized in a small subset of mESCs. Transcriptome analysis indicates that KLF3‐positive mESCs upregulate genes that are initially activated in 8‐cell embryos. Consistently, KLF3 protein but not mRNA is dramatically increased in 8‐cell embryos. Forced expression of KLF3 protein in mESCs promotes the expression of 8‐cell‐embryo activated genes.ConclusionsOur study identifies previously unrecognized heterogeneity due to KLF3 protein expression in mESCs.

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Details

Published: Sep 29, 2020
Vol/Issue: 53(11)
License: View

Authors

J

Jing Hao

Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine Peking University Beijing China

X

Xi Yang

Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine Peking University Beijing China

C

Chao Zhang

Academy for Advanced Interdisciplinary Studies Peking University Beijing China

X

Xue‐Tao Zhang

Academy for Advanced Interdisciplinary Studies Peking University Beijing China

M

Ming Shi

Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine Peking University Beijing China

S

Shao‐Hua Wang

Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine Peking University Beijing China

L

Li Mi

Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine Peking University Beijing China

Y

Yu‐Ting Zhao

Academy for Advanced Interdisciplinary Studies Peking University Beijing China

H

Huiqing Cao

Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine Peking University Beijing China

Y

Yangming Wang

Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine Peking University Beijing China

Funding

National Natural Science Foundation of China Award: 31821091

Cite This Article

Jing Hao, Xi Yang, Chao Zhang, et al. (2020). KLF3 promotes the 8‐cell‐like transcriptional state in pluripotent stem cells. Cell Proliferation, 53(11). https://doi.org/10.1111/cpr.12914

KLF3 promotes the 8‐cell‐like transcriptional state in pluripotent stem cells

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