Journal
CELL REPORTS
Volume 23, Issue 7, Pages 2168-2174Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.04.049
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Funding
- NIH [1R01HL132225, 1R01 HL130840, 1R01HL128072, 1R01HL113601, R01HL065484, R01HL086879, R01HL106579, R01HL108735, 5P30AR061303, 5P30CA030199]
- National Science Foundation (NSF) [STC-0939370]
- Fondation Leducq (Shapeheart)
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Understanding the mechanisms that control human cardiomyocyte proliferation might be applicable to regenerative medicine. We screened a whole genome collection of human miRNAs, identifying 96 to be capable of increasing proliferation (DNA synthesis and cytokinesis) of human iPSC-derived cardiomyo-cytes. Chemical screening and computational approaches indicated that most of these miRNAs (67) target different components of the Hippo pathway and that their activity depends on the nuclear translocation of the Hippo transcriptional effector YAP. 53 of the 67 miRNAs are present in human iPSC cardio-myocytes, yet anti-miRNA screening revealed that none are individually essential for basal proliferation of hiPSC cardiomyocytes despite the importance of YAP for proliferation. We propose a model in which multiple endogenous miRNAs redundantly suppress Hippo signaling to sustain the cell cycle of immature cardiomyocytes.
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