Abstract
Proper placentation is fundamental to successful pregnancy. Placenta arises from differentiation of trophoblast stem (TS) cells during development. Despite being recognized as the counterpart of ES cells in placental development, the role of regulatory miRNAs in TS cell differentiation remains inadequately explored. Here, we have identified complete repertoire of microRNAs present in mouse trophoblast cells in proliferative and differentiated state. We demonstrated that two miRNA clusters, -290 and -322, displayed reciprocal expression during trophoblast differentiation. Loss of miR-290 cluster members or gain in miR-322 cluster members led to differentiation of TS cells. The trophoblast stemness factor, CDX2, transactivated the miR-290 cluster and Cyclin D1 MiR-290 cluster members repressed cell cycle repressors, P21, P27, WEE1, RBL2, and E2F7, in TS cells. MiR-322 cluster members repressed the cell cycle activators, CYCLIN D1, CYCLIN E1, CDC25B, and CDX2, to induce differentiation. Taken together, our findings highlight the importance of posttranscriptional regulation by conserved miRNA clusters that form a regulatory network with CDX2, cell cycle activators, and repressors in equipoising TS cell self-renewal and differentiation.
Highlights
In Eutherian mammals, the placenta provides the physiological interface between the mother and the fetus and is the sole regulator of nutrient and oxygen supply to the developing embryo
94 miRNAs were more abundant in trophoblast stem (TS) cells and were down-regulated upon differentiation (Table S1), whereas 75 miRNAs were poorly expressed in TS cells and were up-regulated in differentiated trophoblast cells (Table S2)
The star or passenger strands of miRNA members of these two clusters and the members which do not have any relevant cell cycle regulator as their target were excluded from this study (Table S3, only the miRNAs written in bold were selected for further study)
Summary
In Eutherian mammals, the placenta provides the physiological interface between the mother and the fetus and is the sole regulator of nutrient and oxygen supply to the developing embryo. Placental functions are primarily executed by various lineages of trophoblast cells, which constitute the main structural component of the placenta (Soares et al, 1996; Roberts et al, 2004; Cross, 2005). The precursor of these differentiated trophoblast lineages is multipotent trophoblast stem (TS) cells, which originate from the trophectoderm layer of the blastocyst (Tanaka et al, 1998). Murine TS cells (Tanaka et al, 1998) are an excellent model to analyze molecular regulation of trophoblast cell differentiation ex vivo
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
