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Publication : FAM122A Is Required for Mesendodermal and Cardiac Differentiation of Embryonic Stem Cells.

First Author  Yang YS Year  2023
Journal  Stem Cells Volume  41
Issue  4 Pages  354-367
PubMed ID  36715298 Mgi Jnum  J:337007
Mgi Id  MGI:7493559 Doi  10.1093/stmcls/sxad008
Citation  Yang YS, et al. (2023) FAM122A Is Required for Mesendodermal and Cardiac Differentiation of Embryonic Stem Cells. Stem Cells 41(4):354-367
abstractText  Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved housekeeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multifaceted physiological and pathological processes. However, the in vivo function of FAM122A is largely unknown. In this study, we observed that Fam122 deletion resulted in embryonic lethality with severe defects of cardiovascular developments and significantly attenuated cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impaired mesendodermal specification and cardiac differentiation from mouse embryonic stem cells but showed no influence on pluripotent identity. Mechanical investigation revealed that the impaired differentiation potential was caused by the dysregulation of histone modification and Wnt and Hippo signaling pathways through modulation of PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This research not only significantly extends our understanding of the regulatory network of mesendodermal/cardiac differentiation but also proposes the potential significance of FAM122A in cardiac regeneration.
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