Transcriptomics

Dataset Information

0

Massive Expansion of Functional Human iPSC-derived Cardiomyocytes by Concomitant Glycogen Synthase Kinase-3 Beta Inhibition and Removal of Cell-Cell Contact


ABSTRACT: Modulating signaling pathways including Wnt and Hippo can induce cardiomyocyte proliferation in vivo. Applying these signaling modulators to human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in vitro can expand CMs only to modest extent (< 5-fold). Here, we demonstrate massive expansion of hiPSC-CMs in vitro (i.e. 100-250-fold) by glycogen synthase kinase-3β (GSK-3β) inhibition using CHIR99021 and concurrent removal of cell-cell contact. We show GSK-3β inhibition suppresses CM maturation while contact removal prevents CMs from cell cycle exit. Remarkably, contact removal enabled 10-to-25-times greater expansion beyond GSK-3β inhibition alone. Mechanistically, cell cycle re-activation required both LEF/TCF activity and AKT phosphorylation, but it was independent from Yes associated protein (YAP) activity. Engineered heart tissues from expanded hiPSC-CMs showed the comparable contractility to those from unexpanded hiPSC-CMs, demonstrating uncompromised cellular functionality after expansion. In sum, we uncovered a molecular interplay that enables massive expansion hiPSC-CMs for large-scale drug screening and tissue engineering.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148586 | GEO | 2020/08/03

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2010-03-26 | GSE21073 | GEO
2021-09-10 | PXD024543 | Pride
2021-10-31 | GSE184125 | GEO
| 2284734 | ecrin-mdr-crc
2014-05-19 | E-GEOD-57781 | biostudies-arrayexpress
2022-08-04 | GSE187308 | GEO
2010-04-07 | E-GEOD-21073 | biostudies-arrayexpress
| PRJNA717225 | ENA
| PRJNA625077 | ENA
| PRJNA126741 | ENA