| First Author | Shanmughapriya S | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 3449 |
| PubMed ID | 30158529 | Mgi Jnum | J:266097 |
| Mgi Id | MGI:6208915 | Doi | 10.1038/s41467-018-05856-4 |
| Citation | Shanmughapriya S, et al. (2018) FOXD1-dependent MICU1 expression regulates mitochondrial activity and cell differentiation. Nat Commun 9(1):3449 |
| abstractText | Although many factors contribute to cellular differentiation, the role of mitochondria Ca(2+) dynamics during development remains unexplored. Because mammalian embryonic epiblasts reside in a hypoxic environment, we intended to understand whether mCa(2+) and its transport machineries are regulated during hypoxia. Tissues from multiple organs of developing mouse embryo evidenced a suppression of MICU1 expression with nominal changes on other MCU complex components. As surrogate models, we here utilized human embryonic stem cells (hESCs)/induced pluripotent stem cells (hiPSCs) and primary neonatal myocytes to delineate the mechanisms that control mCa(2+) and bioenergetics during development. Analysis of MICU1 expression in hESCs/hiPSCs showed low abundance of MICU1 due to its direct repression by Foxd1. Experimentally, restoration of MICU1 established the periodic cCa(2+) oscillations and promoted cellular differentiation and maturation. These findings establish a role of mCa(2+) dynamics in regulation of cellular differentiation and reveal a molecular mechanism underlying this contribution through differential regulation of MICU1. |
