ArticleStem cell research & therapy2024
HAND factors regulate cardiac lineage commitment and differentiation from human pluripotent stem cells.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- Article
- Emerging genes implicated in human congenital heart disease: a 2023-2025 scoping review.Translational pediatrics · 2026Review
- In situ graphene-seq: spatial transcriptomics and chronic electrophysiological characterization of tissue microenvironments.Nature communications · 2026Article
- Rare TruncatingGenes · 2026Article
- Characterization of an induced pluripotent stem cell line NCHi025-A from a 1-year-old female with pulmonary stenosis harboring a heterozygous HAND2 variant.Stem cell research · 2025Article
- Article
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14 authors.
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Abstract
backgroundTranscription factors HAND1 and HAND2 (HAND1/2) play significant roles in cardiac organogenesis. Abnormal expression and deficiency of HAND1/2 result in severe cardiac defects. However, the function and mechanism of HAND1/2 in regulating human early cardiac lineage commitment and differentiation are still unclear.
methodsWith NKX2.5
resultsEither HAND1 or HAND2 knockout did not affect the cardiomyocyte differentiation kinetics, whereas depletion of HAND1/2 resulted in delayed differentiation onset. HAND1 knockout biased cardiac mesoderm toward second heart field progenitors at the expense of first heart field progenitors, leading to increased expression of atrial and outflow tract cardiomyocyte markers, which was further confirmed by the appearance of atrial-like action potentials. By contrast, HAND2 knockout cardiomyocytes had reduced expression of atrial cardiomyocyte markers and displayed ventricular-like action potentials. HAND1/2-deficient hESCs were more inclined to second heart field lineage and its derived cardiomyocytes with atrial-like action potentials than HAND1 single knockout during differentiation. Further mechanistic investigations suggested TBX5 as one of the downstream targets of HAND1/2, whose overexpression partially restored the abnormal cardiomyocyte differentiation in HAND1/2-deficient hESCs.
conclusionsHAND1/2 have specific and redundant roles in cardiac lineage commitment and differentiation. These findings not only reveal the essential function of HAND1/2 in cardiac organogenesis, but also provide important information on the pathogenesis of HAND1/2 deficiency-related congenital heart diseases, which could potentially lead to new therapeutic strategies.
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