Zfp322a Regulates Mouse ES Cell Pluripotency and Enhances Reprogramming Efficiency

Hui Ma, Hui Min Ng, Xiuwen Teh, Hu Li, Yun Hwa Lee, Yew Mei Chong, Yuin Han Loh, James J. Collins, Bo Feng, Henry Yang, Qiang Wu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Embryonic stem (ES) cells derived from the inner cell mass (ICM) of blastocysts are characterised by their ability to self-renew and their potential to differentiate into many different cell types. Recent studies have shown that zinc finger proteins are crucial for maintaining pluripotent ES cells. Mouse zinc finger protein 322a (Zfp322a) is expressed in the ICM of early mouse embryos. However, little is known regarding the role of Zfp322a in the pluripotency maintenance of mouse ES cells. Here, we report that Zfp322a is required for mES cell identity since depletion of Zfp322a directs mES cells towards differentiation. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription. These data along with the results obtained from our ChIP-seq experiment showed that Zfp322a is an essential component of mES cell transcription regulatory network. Targets which are directly regulated by Zfp322a were identified by correlating the gene expression profile of Zfp322a RNAi-treated mES cells with the ChIP-seq results. These experiments revealed that Zfp322a inhibits mES cell differentiation by suppressing MAPK pathway. Additionally, Zfp322a is found to be a novel reprogramming factor that can replace Sox2 in the classical Yamanaka's factors (OSKM). It can be even used in combination with Yamanaka's factors and that addition leads to a higher reprogramming efficiency and to acceleration of the onset of the reprogramming process. Together, our results demonstrate that Zfp322a is a novel essential component of the transcription factor network which maintains the identity of mouse ES cells.

Original languageEnglish (US)
Article numbere1004038
JournalPLoS Genetics
Volume10
Issue number2
DOIs
StatePublished - Feb 2014

Fingerprint

zinc finger motif
Zinc Fingers
embryonic stem cells
zinc
stem
protein
mice
Proteins
proteins
Chromatin Immunoprecipitation
chromatin
Embryonic Stem Cells
cells
cell differentiation
Cell Differentiation
Mouse Embryonic Stem Cells
Blastocyst Inner Cell Mass
transcription (genetics)
Pluripotent Stem Cells
Cellular Structures

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)
  • Medicine(all)

Cite this

Zfp322a Regulates Mouse ES Cell Pluripotency and Enhances Reprogramming Efficiency. / Ma, Hui; Ng, Hui Min; Teh, Xiuwen; Li, Hu; Lee, Yun Hwa; Chong, Yew Mei; Loh, Yuin Han; Collins, James J.; Feng, Bo; Yang, Henry; Wu, Qiang.

In: PLoS Genetics, Vol. 10, No. 2, e1004038, 02.2014.

Research output: Contribution to journalArticle

Ma, H, Ng, HM, Teh, X, Li, H, Lee, YH, Chong, YM, Loh, YH, Collins, JJ, Feng, B, Yang, H & Wu, Q 2014, 'Zfp322a Regulates Mouse ES Cell Pluripotency and Enhances Reprogramming Efficiency', PLoS Genetics, vol. 10, no. 2, e1004038. https://doi.org/10.1371/journal.pgen.1004038
Ma, Hui ; Ng, Hui Min ; Teh, Xiuwen ; Li, Hu ; Lee, Yun Hwa ; Chong, Yew Mei ; Loh, Yuin Han ; Collins, James J. ; Feng, Bo ; Yang, Henry ; Wu, Qiang. / Zfp322a Regulates Mouse ES Cell Pluripotency and Enhances Reprogramming Efficiency. In: PLoS Genetics. 2014 ; Vol. 10, No. 2.
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