1.BMP4 preserves the developmental potential of mESCs through Ube2s- and Chmp4b-mediated chromosomal stability safeguarding.
Mingzhu WANG ; Kun ZHAO ; Meng LIU ; Mengting WANG ; Zhibin QIAO ; Shanru YI ; Yonghua JIANG ; Xiaochen KOU ; Yanhong ZHAO ; Jiqing YIN ; Tianming LI ; Hong WANG ; Cizhong JIANG ; Shaorong GAO ; Jiayu CHEN
Protein & Cell 2022;13(8):580-601
Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals
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Bone Morphogenetic Protein 4/metabolism*
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Cell Differentiation
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Chromosomal Instability
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Endosomal Sorting Complexes Required for Transport
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Mice
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Mitogen-Activated Protein Kinase Kinases/metabolism*
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Mouse Embryonic Stem Cells/cytology*
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Pluripotent Stem Cells/cytology*
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Signal Transduction
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Ubiquitin-Conjugating Enzymes
2.Nuclear m
Chuan CHEN ; Wenqiang LIU ; Jiayin GUO ; Yuanyuan LIU ; Xuelian LIU ; Jun LIU ; Xiaoyang DOU ; Rongrong LE ; Yixin HUANG ; Chong LI ; Lingyue YANG ; Xiaochen KOU ; Yanhong ZHAO ; You WU ; Jiayu CHEN ; Hong WANG ; Bin SHEN ; Yawei GAO ; Shaorong GAO
Protein & Cell 2021;12(6):455-474
N
3.Correction to: Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos.
Chuan CHEN ; Wenqiang LIU ; Jiayin GUO ; Yuanyuan LIU ; Xuelian LIU ; Jun LIU ; Xiaoyang DOU ; Rongrong LE ; Yixin HUANG ; Chong LI ; Lingyue YANG ; Xiaochen KOU ; Yanhong ZHAO ; You WU ; Jiayu CHEN ; Hong WANG ; Bin SHEN ; Yawei GAO ; Shaorong GAO
Protein & Cell 2022;13(6):470-471
4.Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm.
Kuisheng LIU ; Xiaocui XU ; Dandan BAI ; Yanhe LI ; Yalin ZHANG ; Yanping JIA ; Mingyue GUO ; Xiaoxiao HAN ; Yingdong LIU ; Yifan SHENG ; Xiaochen KOU ; Yanhong ZHAO ; Jiqing YIN ; Sheng LIU ; Jiayu CHEN ; Hong WANG ; Yixuan WANG ; Wenqiang LIU ; Shaorong GAO
Protein & Cell 2023;14(4):262-278
Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy
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Female
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Animals
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Mice
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Tetraploidy
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Blastocyst
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Embryo, Mammalian
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Cell Differentiation
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Embryonic Development