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BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways
Open accessAbstract
The fate of pluripotent stem cells is tightly controlled during early embryonic development. Both the derivation and the maintenance of embryonic stem cells (ES cells) in vitro depend on feeder cell-derived growth factors that are largely unidentified. To dissect the mechanisms governing pluripotency, we conducted a screen to identify factors that are produced by mouse embryonic fibroblast STO cells and are required to maintain the pluripotency of ES cells. One of the factors is bone morphogenetic protein 4 (BMP4). Unexpectedly, the major effect of BMP4 on the self-renewal of ES cells is accomplished by means of the inhibition of both extracellular receptor kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways, and inhibitors of ERK and p38 MAPKs mimic the effect of BMP4 on ES cells. Importantly, inhibition of the p38 MAPK pathway by SB203580 overcomes the block in deriving ES cells from blastocysts lacking a functional Alk3 , the BMP type IA receptor. These results uncover a paradigm for BMP signaling in the biology of pluripotent stem cells.
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Cited by
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Lavoie, H., Gagnon, J., & Therrien, M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0255-7 · Cited by 1,185
Moustakas, A., & Heldin, C.-H. (2005) · Journal of Cell Science · doi:10.1242/jcs.02554 · Cited by 958
LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism
Cartwright, P., McLean, C., Sheppard, A., Rivett, D., Jones, K., & Dalton, S. (2005) · Development · doi:10.1242/dev.01670 · Cited by 758
Roles of TGF-β family signaling in stem cell renewal and differentiation
Watabe, T., & Miyazono, K. (2009) · Cell Research · doi:10.1038/cr.2008.323 · Cited by 428
Forcing Stem Cells to Behave: A Biophysical Perspective of the Cellular Microenvironment
Sun, Y., Chen, C. S., & Fu, J. (2012) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-042910-155306 · Cited by 425
Metadata
- Authors
- Qi, X., Li, T.-G., Hao, J., Hu, J., Wang, J., Simmons, H., Miura, S., Mishina, Y., & Zhao, G.-Q.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-04-09
- Volume
- 101
- Issue
- 16
- Pages
- 6027-6032
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2152237832
- Cited by
- 440
- References
- 0
- FWCI
- 12.14
- Type
- journal article
- Language
- en
- Open access
- green
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- Qi, X., Li, T.-G., Hao, J., Hu, J., Wang, J., Simmons, H., Miura, S., Mishina, Y., & Zhao, G.-Q. (2004). BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0401367101
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