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journal article·2025-02Open access

Capture of Totipotency in Mouse Embryonic Stem Cells in the Absence of Pdzk1

Wenhao Zhang, Yiding Zhao, Zhe Yang, Jing Yan, Haisong Wang, Shaochen Nie, Qingshen Jia, Dan Ding, Chao Tong, Xiao‐Ou Zhang, Qian Gao, Ling Shuai

Advanced Science· Volume 12· Issue 6
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Abstract

Abstract Totipotent cells can differentiate into three lineages: the epiblast, primitive endoderm, and trophectoderm. Naturally, only early fertilized embryos possess totipotency, and they lose this ability as they develop. The expansion of stem cell differentiation potential has been a hot topic in developmental biology for years, particularly with respect to the generation totipotent‐like stem cells. Here, the study describes the establishment of totipotency in embryonic stem cells (ESCs) via the deletion of a single gene, Pdzk1 . Pdzk1 ‐knockout (KO) ESCs substantially contribute to the fetus, placenta, and yolk sac in chimera assays but can also self‐organize to form standard blastocyst‐like structures containing the three lineages efficiently; thus, they exhibit full developmental potential as early blastomeres. Single‐cell transcriptome and bulk RNA‐seq comprehensive analyses revealed that Pdzk1 ‐KO activates several lineage inducers ( C1qa , C1qb , Fgf5 , and Cdx2 ) to break down barriers between embryonic and extraembryonic tissues, making these lineages switch smoothly and resulting in a totipotent‐like state. This versatile and scalable system provides a robust experimental model for differentiation potency and cell fate studies.
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Research context

OpenAlex topics: Pluripotent Stem Cells Research · Single-cell and spatial transcriptomics · CRISPR and Genetic Engineering

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Affiliations

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai Animal Resources Center and Reproductive Regulation Institute of Transplantation Medicine Nankai University Tianjin 300350 China

Shanghai Key Laboratory of Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Frontier Science Center for Stem Cell Research School of Life and Science and Technology Tongji University Shanghai 200092 China

Reproductive Medical Center Henan Key Laboratory of Reproduction and Genetics The First Affiliated Hospital of Zhengzhou University Henan 450052 China

National Clinical Research Center for Child Health and Disorders Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical University Chongqing 401122 China

Tianjin Key Laboratory of Animal and Plant Resistance College of Life Sciences Tianjin Normal University Tianjin 300387 China

Funding

National Key Research and Development Program of China · Fundamental Research Funds for the Central Universities · National Natural Science Foundation of China

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