ArticleStem cells translational medicine2026
Effects of increasing intranuclear calcium levels via MCU inhibition on mouse and human PSC-derived cardiomyocyte differentiation and maturation.
Article in Stem cells translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Background Cardiovascular diseases remain the leading cause of death worldwide, accounting for approximately 19.41 million deaths annually. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for disease modeling and therapy. However, variability in differentiation efficiency and maturation state remains a significant challenge. Calcium signaling plays a pivotal role in cardiac differentiation and maturation, with mitochondrial calcium dynamics closely linked to transcriptional activation. Recent evidence suggests that closure of the mitochondrial permeability transition pore promotes cardiomyocyte differentiation by stabilizing calcium homeostasis and reducing oxidative stress. Methods We investigated the effect of 7-aminoindole (7-AI), a mitochondrial calcium uniporter inhibitor, on cardiomyocyte differentiation. Mouse embryonic stem cells and hiPSCs were treated with 7-AI during the cardiac progenitor stage (day 4). Nuclear calcium levels, Ca2+/calmodulin-dependent protein kinase (CaMK) activation, CREB phosphorylation, and cardiac marker expression were assessed. Results 7-AI increased nuclear calcium levels, activated CaMK and CREB, and upregulated cardiac-specific markers, including cTnT, α-SA, and MYH6/7. The resulting cardiomyocytes exhibited improved sarcomere organization and enhanced contractility. Moreover, CREB-deficient cells failed to exhibit these effects, confirming that CREB activation is essential for 7-AI-mediated cardiac maturation. Conclusions Collectively, our findings demonstrate that inhibition of mitochondrial calcium influx redistributes calcium to the nucleus, thereby activating the CaMK-CREB signaling axis and promoting cardiomyocyte differentiation. Targeting mitochondrial calcium handling at the cardiac progenitor stage provides a mechanistic and pharmacological approach to enhance the structural and functional maturation of cardiomyocytes for therapeutic application.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.