Activin A and BMP4 Signaling Expands Potency of Mouse Embryonic Stem Cells in Serum-Free Media.
Stem cell reports
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Wu, B., Li, L., Li, B., Gao, J., Chen, Y., Wei, M., Yang, Z., et al. (2020). Activin A and BMP4 Signaling Expands Potency of Mouse Embryonic Stem Cells in Serum-Free Media.. Stem cell reports, 14 (2), 241-255. https://doi.org/10.1016/j.stemcr.2020.01.004
Inhibitors of Mek1/2 and Gsk3β, known as 2i, and together with leukemia inhibitory factor, enhance the derivation of embryonic stem cells (ESCs) and promote ground-state pluripotency (2i/L-ESCs). However, recent reports show prolonged Mek1/2 suppression impairs developmental potential of ESCs, and is rescued by serum (S/L-ESCs). Here we show that culturing ESCs in Activin A, BMP4 and in the absence of MEK1/2 inhibitor (ABC/L medium) establishes advanced stem cells derived from ESCs (esASCs). We demonstrate that esASCs contributed to germline lineages, full term chimeras and generated esASCs-derived mice by tetraploid complementation. We show that in contrast to 2i/L-ESCs, esASCs display distinct molecular signatures and stable hypermethylated epigenome which is reversible and similar to serum cultured ESCs. Importantly, we also derived novel ASCs (blASCs) from blastocysts in ABC/L medium. Our results provide insights into the derivation of novel ESCs with DNA hypermethylation from blastocysts in chemically defined medium.
Wellcome Trust (209475/Z/17/Z)
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External DOI: https://doi.org/10.1016/j.stemcr.2020.01.004
This record's URL: https://www.repository.cam.ac.uk/handle/1810/301711
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