2. Academic Validation
  3. Rif1 and Hmgn3 regulate the conversion of murine trophoblast stem cells

Rif1 and Hmgn3 regulate the conversion of murine trophoblast stem cells

  • Cell Rep. 2022 Mar 29;38(13):110570. doi: 10.1016/j.celrep.2022.110570.
Wenhao Zhang 1,  Chunmeng Yao 2,  Yanrui Luo 3,  Qian Li 3,  Qian Zhao 3,  Yiding Zhao 2,  Yuna Wang 2,  Mengyang Geng 2,  Qing Wang 2,  Mei Xu 2,  Shengyi Sun 2,  Dan Wu 2,  Qian Gao 2,  Xudong Wu 4,  Ling Shuai 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300350, China; Chongqing Key Laboratory of Human Embryo Engineering, Chongqing Health Center for Women and Children, Chongqing 400013, China.
  • 2 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300350, China.
  • 3 State Key Laboratory of Experimental Hematology, Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Tianjin 300070, China.
  • 4 State Key Laboratory of Experimental Hematology, Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Tianjin 300070, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300350, China; Tianjin Central Hospital of Gynecology Obstetrics/Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin 300052, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China. Electronic address: [email protected].
PMID: 35354046 DOI: 10.1016/j.celrep.2022.110570
Abstract

The appearance of trophectoderm (TE) is a hallmark event in preimplantation development during murine embryogenesis. However, little is known about the mechanisms underlying TE specification. We find that the depletion of Rif1 breaks down the barrier to the transition from embryonic stem cells (ESCs) to trophoblast stem cells (TSCs). Rif1-null-induced TSCs show typical TE properties and the potential to differentiate into terminal trophoblast lineages. Global transcriptome analysis reveal that Rif1 deletion activates 2-cell embryo (2C)-related genes and induces a totipotent-like state. Chimeric assays further confirm that Rif1-null ESCs contribute to the functional placenta in addition to the fetus on embryonic day 12.5. Furthermore, we show overexpression of Hmgn3, one of the key upregulated gene in Rif1-null ESCs, facilitates the induction of TSCs. Therefore, we report two key genes regulating the conversion of TSCs and provide insights for investigating TE specification.

Keywords

2C-related genes; CP: Molecular biology; CP: Stem cell research; Hmgn3; Rif1; TE specification; totipotent-like status.

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