miRNAs that Induce Human Cardiomyocyte Proliferation Converge on the Hippo Pathway

Cell Reports
Marta Diez-CuñadoMark Mercola

Abstract

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 cardiomyocytes. 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 cardiomyocytes, 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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Datasets Mentioned

BETA
GSE60293
GSE60291
GSE60292
GSE111984

Methods Mentioned

BETA
transfection
flow cytometry
nuclear translocation
RNA-seq

Software Mentioned

miRSystem
GE Healthcare Software Developer Toolbox
DAVID
Database for Annotation , Visualization and Integrated Discove...
CyteSeer

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