2. Academic Validation
  3. Haploid-genetic screening of trophectoderm specification identifies Dyrk1a as a repressor of totipotent-like status

Haploid-genetic screening of trophectoderm specification identifies Dyrk1a as a repressor of totipotent-like status

  • Sci Adv. 2023 Dec 22;9(51):eadi5683. doi: 10.1126/sciadv.adi5683.
Wenhao Zhang 1,  Shengyi Sun 1,  Qing Wang 1,  Xu Li 1 2,  Mei Xu 1,  Qian Li 3,  Yiding Zhao 1,  Keli Peng 1,  Chunmeng Yao 1,  Yuna Wang 1,  Ying Chang 1,  Yan Liu 4,  Xudong Wu 3,  Qian Gao 1,  Ling Shuai 1 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy and Tianjin Central Hospital of Gynecology Obstetrics/Tianjin Key Laboratory of Human Development and Reproductive Regulation, Nankai University, Tianjin 300350, China.
  • 2 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 3 State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Tianjin 300070, China.
  • 4 Department of Obstetrics, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China.
  • 5 National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
PMID: 38117886 DOI: 10.1126/sciadv.adi5683
Abstract

Trophectoderm (TE) and the inner cell mass are the first two lineages in murine embryogenesis and cannot naturally transit to each other. The barriers between them are unclear and fascinating. Embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) retain the identities of inner cell mass and TE, respectively, and, thus, are ideal platforms to investigate these lineages in vitro. Here, we develop a loss-of-function genetic screening in haploid ESCs and reveal many mutations involved in the conversion of TSCs. The disruption of either Catip or Dyrk1a (candidates) in ESCs facilitates the conversion of TSCs. According to transcriptome analysis, we find that the repression of Dyrk1a activates totipotency, which is a possible reason for TE specification. Dyrk1a-null ESCs can contribute to embryonic and extraembryonic tissues in chimeras and can efficiently form blastocyst-like structures, indicating their totipotent developmental abilities. These findings provide insights into the mechanisms underlying cell fate alternation in embryogenesis.

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