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Data · study · 2026

Depletion of IRX3 promotes early cardiac commitment and maturation of human Ipsc-derived cardiomyocytes

Listed in NCBI GEO

The limited regenerative capacity of the adult human heart makes human induced pluripotent stem cell (hiPSC)-based therapies a promising approach for treating myocardial infarction.

Description

However, hiPSC-derived cardiomyocytes (hiPSC-CM) display immature features. In this study, we demonstrate that depletion of the transcription factor IRX3 promotes early cardiac commitment and enhances the maturation of hiPSC-CMs.

We first established the temporal expression of IRX3 during hiPSC-CM differentiation and subsequently investigated its role by generating two IRX3 mutant hiPSC lines. IRX3-depleted cardiac progenitors exhibited increased expression of GATA4, NKX2-5, TBX5 and Wnt signaling-related genes, along with increased proliferation. Differentiation of IRX3-depleted cells yielded more cardiomyocytes with enhanced expression of TNNI1 and CX43.

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Notably, IRX3-depleted cardiomyocytes showed improved sarcomere alignment, enhanced cell-to-cell communication, and electrophysiological maturation. Furthermore, in silico analysis suggests that IRX3 regulates cardiomyocyte differentiation by modulating TBX5, GATA4 and NKX2-5 transcription along with their targets. Collectively, our findings underscore the potential of IRX3 depletion in facilitating the molecular and functional development of human cardiomyocytes.

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From keywords
Life Sciences
Inferred from text
Heart 75% · Myocardial infarction 75%
Provenance · 1 source records, 9 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE26277613 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[anatomy].local:anatomy:heartenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[disease].local:disease:myocardial-infarctionenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-arraysource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title