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

Protein Cell, 2022 · DOI: https://doi.org/10.1007/s13238-021-00896-x · Published: August 1, 2022

Simple Explanation

Mouse embryonic stem cells (mESCs) are derived from the inner cell mass (ICM) of the developing blastocyst and have the abilities of self-renewal and pluripotency to reconstitute embryonic lineages. The impaired 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. 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.

Study Duration

Not specified

Participants

Mouse embryonic stem cells (mESCs)

Evidence Level

Not specified

Key Findings

1
BMP4 activation can preserve the developmental potential and safeguard the chromosomal integrity of mESCs.
2
Ube2s and Chmp4b are critical downstream targets of BMP4, both of which are essential for BMP4-mediated chromosomal integrity safeguarding, normal proliferation capacity and developmental potential maintenance of mESCs.
3
BMP4 largely restored critical genes and signal pathways dysregulated under chemically deﬁned condition and could sustain the enhanced developmental potential of mESCs during long-term culture.

Research Summary

This study reveals that the BMP signaling pathway is deﬁcient in the chemically deﬁned 2i condition (N/2i), which greatly impairs the developmental potential of mESCs. Addition of BMP4 in N/2i condition can restore the expression of Ube2s and Chmp4b, which further safeguards chromosomal integrity and largely promotes in vivo differentiation potential of mESCs. Notably, N/2i + BMP4-mESCs possess a better pluripotency over N/a2i- and N/t2i-mESCs. Together, our study reveals a valid role of BMP4 in harnessing the functional pluripotency capacity of mESCs under the chemically deﬁned culture system.

Practical Implications

Improved mESC Culture

BMP4 should be applied in the serum-free culture system to maintain chromosomal integrity and regulate functional pluripotency.

Understanding Pluripotency Regulation

BMP4 plays multiple essential roles in regulating pluripotency, beyond just inhibiting differentiation genes.

Regenerative Medicine Applications

Optimizing culture conditions for pluripotent stem cells is crucial for their use in regenerative medicine.

Study Limitations

1
How BMP4 precisely orchestrates histone modiﬁcations at the promoter regions of Ube2s and Chmp4b remains to be studied.
2
The study primarily focuses on mouse embryonic stem cells, and the findings may not be directly transferable to human ESCs.
3
While the study identifies Ube2s and Chmp4b as key downstream targets of BMP4, other potential targets and pathways may also contribute to the observed effects.

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