Transcriptomic analysis of hiPSC-derived cardiomyocytes uncovers key maturation signalling pathways
November 2021
A*STAR Institute of Molecular and Cell Biology, Singapore, Singapore
Human pluripotent stem-cell-derived cardiomyocytes represent an exciting tool for disease modelling and cell therapy. However, there are still severe limitations in their applications. Here, a human hexokinase1-GFP metabolic reporter cell line was used to discriminate between fetal and mature phenotypes of differentiated cardiomyocytes and perform transcriptomic analysis to identify key gene regulatory pathways involved in cardiomyocyte maturation. The results showed that the interferon-signalling pathway was differentially regulated between both cell types. Furthermore, cardiomyocytes treated with Interferon-gamma had increased JAK-STAT signalling and improved maturation, both in gene expression profiles and functional physiological outcomes. Consequently, inhibition of the JAK-STAT pathway with ruxolitinib resulted in the inhibition of these functional improvements. Overall, the researchers uncover key regulatory pathways implicated in vitro in human cardiomyocytes maturation which could be potentially used to improve differentiation protocols and increase the relevance of stem cell-based cardiac models.
Upregulation of the JAK-STAT pathway promotes maturation of human embryonic stem cell-derived cardiomyocytes
Boon-Seng Soh, Shi-Yan Ng
Added on: 11-29-2021
[1] https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00544-0
