2. Academic Validation
  3. Dppa3 Improves the Germline Competence of Pluripotent Stem Cells

Dppa3 Improves the Germline Competence of Pluripotent Stem Cells

  • Stem Cell Rev Rep. 2023 May 12. doi: 10.1007/s12015-023-10552-y.
Siying Liu # 1 2,  Shuang Zhao # 1 3,  Chuanyu Zhang # 1,  Chenglei Tian # 3,  Dan Wang 1 4,  Huaxin Yu 1,  Zongjin Li 1,  Lin Liu 5 6,  Na Liu 7 8
Affiliations

Affiliations

  • 1 School of Medicine, Nankai University, Tianjin, 300071, China.
  • 2 Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences Nankai University, Tianjin, 300071, China.
  • 3 College of Life Sciences, Nankai University, Tianjin, 300071, China.
  • 4 MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
  • 5 Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences Nankai University, Tianjin, 300071, China. liulin@nankai.edu.cn.
  • 6 College of Life Sciences, Nankai University, Tianjin, 300071, China. liulin@nankai.edu.cn.
  • 7 School of Medicine, Nankai University, Tianjin, 300071, China. liuna@nankai.edu.cn.
  • 8 Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences Nankai University, Tianjin, 300071, China. liuna@nankai.edu.cn.
  • # Contributed equally.
PMID: 37171679 DOI: 10.1007/s12015-023-10552-y
Abstract

Background: Chimera formation and germline competence are critical features of mouse pluripotent stem cells (PSCs). However, the factors that contribute to germline competence in the chimeras remain to be understood.

Methods: To determine the role of Dppa3 in PSCs, we first constructed Dppa3 knockout (Dppa3 KO) and Dppa3 overexpression (Dppa3 OE) PSCs, respectively. Using Dppa3 KO and Dppa3 OE PSCs, we then investigated the role of Dppa3 in PSCs by evaluating the chimera generation, DNA methylation, and pluripotent state conversion.

Results: We show that Dppa3 plays an important role in chimera formation and germline competence of mouse PSCs. PSC lines with high expression of Dppa3 show high germline competence. In contrast, Dppa3 deficiency reduces chimera formation and abrogates the germline transmission capacity of PSCs. Molecularly, Dppa3 facilitates establishing global DNA hypomethylation in PSCs. High levels of Dppa3 in PSCs reduce the expression of Dnmt3a/b and impede Uhrf1-Dnmt1 complex binding to DNA replication forks, maintaining DNA hypomethylation. Additionally, Dppa3 facilitates two-cell-stage (2C) genes expression and promotes conversion to a 2C-like state.

Conclusion: These data show that Dppa3 is involved in maintaining DNA hypomethylation homeostasis and is required for high chimera formation and germline competence of PSCs.

Keywords

DNA methylation; Dppa3; Germline competency; Pluripotent stem cells.

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