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Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE299579 | GEO | 2025/09/10

REPOSITORIES: GEO

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Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects [scRNA-seq]

Project description:The bHLH transcription factors HAND1 and HAND2 are expressed in partially overlapping patterns during development. Studies have established evidence for significant functional redundancy between HAND1 and HAND2. To test redundancy fully, we engineered a Hand1 allele where we directly replace the exons and intron with those of Hand2. Results show that 2% of Hand1Hand2/ Hand2 mice are viable, and fertile. The remaining Hand1Hand2/Hand2 embryos exhibit neonatal lethality due to omphalocele, ventricular septal defects and conduction anomalies. Omphalocele can occur due to altered gut rotation and transcriptomic expression analysis reveals that established gene expression patterns associated with normal gut rotation are compromised. Interrogation of cardiac function in surviving Hand1Hand2/Hand2 mice reveals QRS abnormalities and accompanies cardiac morphogenic defects. These data support previous findings that HAND factors exhibit extensive functional overlap but do reveal that unique functions for HAND1 and HAND2 proteins within the Hand1 expression domain that are required for normal embryonic development.

2025-09-10 | GSE299253 | GEO

Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects [Spatial Transcriptomics]

2025-09-10 | GSE298742 | GEO

Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects

Project description:Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects

| PRJNA1275004 | ENA

Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects [scRNA-seq]

Project description:Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects [scRNA-seq]

| PRJNA1273164 | ENA

Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects [Spatial Transcriptomics]

Project description:Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects [Spatial Transcriptomics]

| PRJNA1271041 | ENA

Hand1 KO HAND2 replacement RNA-Seq data

Project description:This is an analysis of E9.5 mouse yold sacs from control, HAND1 loss-of-function, and HAND2 replacement mice

2025-09-28 | GSE223771 | GEO

HAND1 loss-of-function within the embryonic myocardium reveals survivable congenital cardiac defects and adult heart failure.

Project description:AimsTo examine the role of the basic Helix-loop-Helix (bHLH) transcription factor HAND1 in embryonic and adult myocardium.Methods and resultsHand1 is expressed within the cardiomyocytes of the left ventricle (LV) and myocardial cuff between embryonic days (E) 9.5-13.5. Hand gene dosage plays an important role in ventricular morphology and the contribution of Hand1 to congenital heart defects requires further interrogation. Conditional ablation of Hand1 was carried out using either Nkx2.5 knockin Cre (Nkx2.5Cre) or α-myosin heavy chain Cre (αMhc-Cre) driver. Interrogation of transcriptome data via ingenuity pathway analysis reveals several gene regulatory pathways disrupted including translation and cardiac hypertrophy-related pathways. Embryo and adult hearts were subjected to histological, functional, and molecular analyses. Myocardial deletion of Hand1 results in morphological defects that include cardiac conduction system defects, survivable interventricular septal defects, and abnormal LV papillary muscles (PMs). Resulting Hand1 conditional mutants are born at Mendelian frequencies; but the morphological alterations acquired during cardiac development result in, the mice developing diastolic heart failure.ConclusionCollectively, these data reveal that HAND1 contributes to the morphogenic patterning and maturation of cardiomyocytes during embryogenesis and although survivable, indicates a role for Hand1 within the developing conduction system and PM development.

| S-EPMC7252443 | biostudies-literature

Hand2 loss-of-function in Hand1-expressing cells reveals distinct roles in epicardial and coronary vessel development.

Project description:RationaleThe basic helix-loop-helix (bHLH) transcription factors Hand1 and Hand2 are essential for embryonic development. Given their requirement for cardiogenesis, it is imperative to determine their impact on cardiovascular function.ObjectiveTo deduce the role of Hand2 within the epicardium.Method and resultsWe engineered a Hand1 allele expressing Cre recombinase. Cardiac Hand1 expression is largely limited to cells of the primary heart field, overlapping little with Hand2 expression. Hand1 is expressed within the septum transversum, and the Hand1 lineage marks the proepicardial organ and epicardium. To examine Hand factor functional overlap, we conditionally deleted Hand2 from Hand1-expressing cells. Hand2 mutants display defective epicardialization and fail to form coronary arteries, coincident with altered extracellular matrix deposition and Pdgfr expression.ConclusionsThese data demonstrate a hierarchal relationship whereby transient Hand1 septum transversum expression defines epicardial precursors that are subsequently dependent on Hand2 function.

| S-EPMC3086599 | biostudies-literature

Hand1 KO HAND2 replacement RNA-Seq data

Project description:Hand1 KO HAND2 replacement RNA-Seq data

| PRJNA928357 | ENA

Neonatal Deletion of <i>Hand1</i> and <i>Hand2</i> within Murine Cardiac Conduction System Reveals a Novel Role for HAND2 in Rhythm Homeostasis.

Project description:The cardiac conduction system, a network of specialized cells, is required for the functioning of the heart. The basic helix loop helix factors Hand1 and Hand2 are required for cardiac morphogenesis and have been implicated in cardiac conduction system development and maintenance. Here we use embryonic and post-natal specific Cre lines to interrogate the role of Hand1 and Hand2 in the function of the murine cardiac conduction system. Results demonstrate that loss of HAND1 in the post-natal conduction system does not result in any change in electrocardiogram parameters or within the ventricular conduction system as determined by optical voltage mapping. Deletion of Hand2 within the post-natal conduction system results in sex-dependent reduction in PR interval duration in these mice, suggesting a novel role for HAND2 in regulating the atrioventricular conduction. Surprisingly, results show that loss of both HAND factors within the post-natal conduction system does not cause any consistent changes in cardiac conduction system function. Deletion of Hand2 in the embryonic left ventricle results in inconsistent prolongation of PR interval and susceptibility to atrial arrhythmias. Thus, these results suggest a novel role for HAND2 in homeostasis of the murine cardiac conduction system and that HAND1 loss potentially rescues the shortened HAND2 PR phenotype.

| S-EPMC9324487 | biostudies-literature

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