RESEARCH ARTICLE

BMP4 preserves the developmental potential of mESCs through Ube2s- and Chmp4b-mediated chromosomal stability safeguarding

  • Mingzhu Wang 1,2 ,
  • Kun Zhao 1,2 ,
  • Meng Liu 1,2,3 ,
  • Mengting Wang 1,2 ,
  • Zhibin Qiao 1,2,4 ,
  • Shanru Yi 1,2 ,
  • Yonghua Jiang 5 ,
  • Xiaochen Kou 1,2 ,
  • Yanhong Zhao 1,2 ,
  • Jiqing Yin 1,2 ,
  • Tianming Li 1,2 ,
  • Hong Wang 1 ,
  • Cizhong Jiang , 2,3 ,
  • Shaorong Gao , 1,2,4 ,
  • Jiayu Chen , 1,2
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  • 1. Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
  • 2. Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China
  • 3. Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, Tongji University, Shanghai 200065, China
  • 4. Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200123, China
  • 5. Guangxi Key Laboratory of Genomic and Personalized Medicine, Nanning 530021, China

Published date: 15 Aug 2022

Copyright

2022 The Author(s)

Abstract

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 serumfree culture system.

Cite this article

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 . BMP4 preserves the developmental potential of mESCs through Ube2s- and Chmp4b-mediated chromosomal stability safeguarding[J]. Protein & Cell, 2022 , 13(8) : 580 -601 . DOI: 10.1007/s13238-021-00896-x

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