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Trophoblast cells, recognized as parenchymal cells of placenta, execute most placental functions, indispensible for successful pregnancy. They arise from the trophoblast stem (TS) cell niche during development. TS cells are recognized as the developmental counterpart of ES cells in the context of placental development. Role of regulatory miRNAs in TS cell differentiation remain inadequately explored. Research in our laboratory has unveiled a compendium of miRNAs that are differentially regulated in the trophoblast stem cells and upon induction of their differentiation. We identified two regulatory miRNA clusters and demonstrated that they control cell cycle regulators as well as stemness factor CDX2, effectively forming a regulatory network that equipoise TS cell self renewal and differentiation. We have further deciphered that a) miR-141-3p curbs transthyretin synthesis by trophoblast cells during intra-uterine growth restriction, b) miR-322 and miR-503 regulate mitochondrial metabolism in developing placenta by regulating COX6B2.
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