Dppa3 is Critical for Lin28a-regulated ES Cells Naïve-primed State Conversion

Overview

Journal J Mol Cell Biol

Publisher Oxford University Press

Specialty Molecular Biology

Date 2018 Nov 28

PMID 30481289

Citations 13

Authors

Hui Sang

Dan Wang

Shuang Zhao

Jinxin Zhang

Yan Zhang

Jia Xu

Xiaoniao Chen

Yan Nie

Kaiyue Zhang

Shuaiqiang Zhang

Yuebing Wang

Na Wang

Fengxia Ma

Ling Shuai

Zongjin Li

Na Liu

Affiliations

Soon will be listed here.

Abstract

Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and mechanism in the conversion of ES cells from naïve to primed state remain unclear. Here, we present evidence for Dppa3, a protein originally known for its role in germ cell development, as a downstream target of Lin28a in naïve-primed conversion. Using rescue experiment, we demonstrate that Dppa3 functions predominantly downstream of Lin28a during naïve-primed state conversion. Higher level of Lin28a prevents let-7 maturation and results in Dnmt3a/b (target of let-7) upregulation, which in turn induces hypermethylation of the Dppa3 promoter. Dppa3 demarcates naïve versus primed pluripotency states. These results emphasize that Lin28a plays an important role during the naïve-primed state conversion of ES cells, which is partially mediated by a Lin28a-let-7-Dnmt3a/b-Dppa3 axis.

Citing Articles

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Combinatorial quantification of 5mC and 5hmC at individual CpG dyads and the transcriptome in single cells reveals modulators of DNA methylation maintenance fidelity.

Chialastri A, Sarkar S, Schauer E, Lamba S, Dey S Nat Struct Mol Biol. 2024; 31(8):1296-1308.

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Dynamic nucleolar phase separation influenced by non-canonical function of LIN28A instructs pluripotent stem cell fate decisions.

Tan T, Gao B, Yu H, Pan H, Sun Z, Lei A Nat Commun. 2024; 15(1):1256.

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Evaluation of the determinants for improved pluripotency induction and maintenance by engineered SOX17.

Hu H, Ho D, Tan D, MacCarthy C, Yu C, Weng M Nucleic Acids Res. 2023; 51(17):8934-8956.

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Dppa3 Improves the Germline Competence of Pluripotent Stem Cells.

Liu S, Zhao S, Zhang C, Tian C, Wang D, Yu H Stem Cell Rev Rep. 2023; 19(6):1845-1855.

PMID: 37171679 DOI: 10.1007/s12015-023-10552-y.

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