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The following is a summary of “Transient stabilization of human cardiovascular progenitor cells from human pluripotent stem cells in vitro reflects stage-specific heart development in vivo,” published in the July 2024 issue of Cardiology by Bolesani et al.
Understanding the molecular characteristics of human pluripotent stem cell (hPSC)-derived cardiac progenitors and the mechanisms regulating their proliferation and differentiation proved valuable for developmental biology and regenerative medicine.
Researchers conducted a retrospective study to show that chemical modulation of histone acetyl transferases (by IQ-1) and WNT (by CHIR99021) synergistically enabled the transient and reversible block of directed cardiac differentiation progression on hPSCs.
They characterized the resulting stabilized cardiovascular progenitors (SCPs) by ISL1pos/KI-67pos/NKX2-5neg expression.
The results showed that in the presence of the chemical inhibitors, SCPs maintained a proliferation quiescent state. Upon small molecule removal, SCPs resumed proliferation, and concomitant NKX2-5 up-regulation triggered cell-autonomous differentiation into cardiomyocytes. Directed differentiation of SCPs into the endothelial and smooth muscle lineages confirmed their full developmental potential typical of bona fide cardiovascular progenitors. Single-cell RNA-sequencing-based transcriptional profiling of the in vitro generated human SCPs notably reflected the dynamic cellular composition of E8.25-E9.25 posterior second heart field of mouse hearts, hallmarked by nuclear receptor subfamily 2 group F member 2 expression. Investigating molecular mechanisms of SCP stabilization, they found that the cell-autonomously regulated retinoic acid and BMP signaling governed the SCP transition from quiescence towards proliferation and cell-autonomous differentiation, reminiscent of a niche-like behavior.
They concluded that the stabilization approach’s chemically defined and reversible nature provided an unprecedented opportunity to dissect mechanisms of cardiovascular progenitors’ specification and reveal the cellular and molecular properties.
Source: academic.oup.com/cardiovascres/article/120/11/1295/7688139
