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Totipotency is the ability of a cell to generate a whole organism, a property that characterizes the first embryonic cells, such as the zygote and the blastomeres. This review provides a retrospective on the progress made in the last decade in the study of totipotency, especially with the discovery of mouse ES cells expressing markers of the 2-cell stage (2C-like cells). This model has greatly contributed to a better understanding of the molecular mechanisms involved in totipotency (pioneer factors, epigenetic regulation, splicing, nuclear maturation). 2C-like cells have also paved the way for the development of new cellular models of human totipotency.
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http://dx.doi.org/10.1051/medsci/2023217 | DOI Listing |
Nat Commun
August 2025
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
In mouse, minor zygotic genome activation (ZGA) precedes and is essential for major ZGA in two-cell (2C) embryos. A subset of ZGA genes (known as "2C" genes) are also activated in a rare population of embryonic stem cells (ESCs) (2C-like cells). However, the functions of the 2C genes are not fully understood.
View Article and Find Full Text PDFNucleic Acids Res
June 2025
State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Naïve mouse embryonic stem cells (mESCs) are characterized by a mixed population of cells in an interconvertible pluripotent state and a totipotent 2-cell (2C)-like state. It remains to be understood how the pluripotent state is maintained while the 2C-like state is suppressed. We show that N-acetyltransferase 10 (Nat10) maintains the pluripotent state and suppresses the 2C-like state in mESCs through mRNA modification and stabilization.
View Article and Find Full Text PDFNucleic Acids Res
April 2025
State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
Two-cell-like cells (2CLCs), a rare population (∼0.5%) in mouse embryonic stem cell (mESC) cultures, are in a transient totipotent-like state resembling that of 2C-stage embryos, and their discovery and characterization have greatly facilitated the study of early developmental events, such as zygotic genome activation. However, the molecular determinants governing 2C-like reprogramming remain to be elucidated.
View Article and Find Full Text PDFJ Biol Chem
May 2025
School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, China. Electronic address:
Mouse embryonic stem cells (ESCs) consist of a rare population of heterogeneous 2-cell-like cells (2CLCs). These cells transiently recapitulate the transcriptional and epigenetic features of the 2-cell embryos, serving as a unique model for studying totipotency acquisition and embryonic development. Accumulating evidence has demonstrated that transcription factors and epigenetic modifications exert crucial functions in the transition of ESCs to 2CLCs.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2025
State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
Zygotic genome activation (ZGA) confers to the mouse two-cell (2C) embryo a unique transcriptional profile characterized by transient up-regulation of many totipotency-related genes and retrotransposons. Intriguingly, those genes are duplicated and clustered in the genome during evolution, including cluster, and family members in mice. However, the contribution and biological significance of the totipotency-related gene duplication events in early embryo development remain poorly understood.
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