The transcriptome of hand2 loss- and gain-of-function embryonic cardiomyocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1006302 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25661605.fastq.gz | Fastqsanger.gz | |||
| SRR25661606.fastq.gz | Fastqsanger.gz | |||
| SRR25661607.fastq.gz | Fastqsanger.gz | |||
| SRR25661608.fastq.gz | Fastqsanger.gz | |||
| SRR25661609.fastq.gz | Fastqsanger.gz |
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Project description:To gain mechanistic insight into how Hand2 regulates cardiac fusion, we performed transcriptomic analyses of hand2 loss- and gain-of-function 20 hpf cardiomyocytes.
2024-10-15 | GSE241049 | GEO
Project description:In humans, cardiac hypertrophy is the principal risk factor for the development of overt heart failure and sudden cardiac death from lethal arrhythmias. Although aberrant reactivation of fetal² gene programs is intricately linked to maladaptive hypertrophy of postnatal cardiomyocytes, loss of cardiac function and heart failure, the transcription factors driving these gene programs remain ill defined. We report that the basic helix-loop-helix (bHLH) transcription factor dHAND/Hand2 is re-expressed in the mammalian postnatal myocardium in response to stress signaling. Interestingly, mutant mice overexpressing Hand2 in otherwise healthy ventricular myocytes developed a phenotype of pathological hypertrophy. In contrast, conditional gene-targeted Hand2 mice demonstrated a marked resistance to pressure overload-induced hypertrophy, fibrosis, ventricular dysfunction and induction of a fetal gene program. These data suggest a critical role for the Hand2 transcription factor during hypertrophic remodeling and heart failure. To gain more mechanistically insight in the processes underlying heart failure, we here identified Hand2 target genes by microarray gene expression profiling. RNA samples were collected 4 weeks after sham or TAC surgery (to induce pressure overload) of both tamoxifen-treated Hand2f/f (WT) and MCM-Hand2f/f (KO) mice.
2013-11-15 | E-MTAB-1821 | biostudies-arrayexpress
Project description:Heart formation requires the fusion of bilateral cardiomyocyte populations as they move toward the embryonic midline. The bHLH transcription factor Hand2 is essential for cardiac fusion; however, the effector genes that execute this function of Hand2 are unknown. Here, we provide the first evidence for a downstream component of the Hand2 pathway that mediates cardiac morphogenesis. Although hand2 is expressed in cardiomyocytes, mosaic analysis demonstrates that hand2 plays a non-autonomous role in regulating cardiomyocyte movement. Gene expression profiles reveal heightened expression of fibronectin 1 (fn1) in hand2 mutant embryos. Reciprocally, overexpression of hand2 leads to decreased Fibronectin levels. Furthermore, reduction of fn1 function enables rescue of cardiac fusion in hand2 mutants: bilateral cardiomyocyte populations merge and exhibit improved tissue architecture, albeit without major changes in apicobasal polarity. Together, our data provide a novel example of a tissue creating a favorable environment for its morphogenesis: the Hand2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of Fn1 levels. Embryos from three independent hand2 mutant (hanS6 allele) heterozyogous crosses were collected. Examination of Tg(myl7:egfp) expression allow sorting of hand2 mutant embryos from their wild-type siblings.
2010-08-03 | E-GEOD-23381 | biostudies-arrayexpress
Project description:Investigate the effect of gain of HAND2 on chromatin accessibility.
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Project description:The overexpression of HAND2 in IMR32 cells results in a increase of chromation accessibility at the HAND2 and MYCN common binding sites.
2023-03-29 | GSE184232 | GEO
Project description:The bHLH transcriptional regulator HAND2 performs essential functions during development of the embryonic limb, heart and branchial arches, however, its genomic target regions remained largely unkown. Here, we uncover the range of candidate HAND2 target cis-regulatory modules in the major Hand2 expressing embryonic tissues during midgestation and focus on the transcriptional networks controlled by HAND2 in the developing limb. Our functional and genetic analysis reveals that in the early limb mesenchyme HAND2 directly regulates the expression of several transcription factors involved in the morphogenesis of limb proximal skeletal elements. In addition, HAND2 operates as a key factor in the establishment of anterior and posterior compartments, partly through direct binding to a Gli3 cis-regulatory module. Furthermore, HAND2 refines the posterior boundary of Gli3 expression domain through a relay mechanism mediated by Tbx3. These HAND2-dependent regulatory interactions are required to set the boundaries defining the localized expression of the Shh organizer region, which allows progression of distal limb outgrowth.
2014-11-11 | GSE55707 | GEO
Project description:Heart formation requires the fusion of bilateral cardiomyocyte populations as they move toward the embryonic midline. The bHLH transcription factor Hand2 is essential for cardiac fusion; however, the effector genes that execute this function of Hand2 are unknown. Here, we provide the first evidence for a downstream component of the Hand2 pathway that mediates cardiac morphogenesis. Although hand2 is expressed in cardiomyocytes, mosaic analysis demonstrates that hand2 plays a non-autonomous role in regulating cardiomyocyte movement. Gene expression profiles reveal heightened expression of fibronectin 1 (fn1) in hand2 mutant embryos. Reciprocally, overexpression of hand2 leads to decreased Fibronectin levels. Furthermore, reduction of fn1 function enables rescue of cardiac fusion in hand2 mutants: bilateral cardiomyocyte populations merge and exhibit improved tissue architecture, albeit without major changes in apicobasal polarity. Together, our data provide a novel example of a tissue creating a favorable environment for its morphogenesis: the Hand2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of Fn1 levels.
2010-08-03 | GSE23381 | GEO
Project description:HAND2 regulates regional chromation modification [HAND2-knockdown_histone_ChIPseq]
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Project description:Our previous study revealed that the basic helix-loop-helix transcription factor Hand2 is a downstream target of progesterone signaling in mouse uterine stroma at the time of implantation. Further, conditional deletion of Hand2 in mouse uterus leads to implantation failure due to impaired uterine epithelial receptivity. To identify the downstream targets of Hand2 in the uterus, we performed gene expression profling of uterine stromal cells isolated from Hand2-null mice and the corresponding controls on day4 of pregnancy (the time of implantation). The microarray results revealed elevated expression of mRNAs corresponding to several members of the fibroblast growth factor family in uterine stroma of Hand2-ablated mice. These factors act as paracrine mediators of mitogenic effects of estrogen on the epithleium. Thus, Hand2 is a critical regulator of the uteirne stromal-epithelial communication that directs proper steroid regulation conducive for establshment of pregnancy. We performed conditional ablation of Hand2 in the mouse uterus using the PRcre mouse model. As Hand2 expression is restricted to stromal comaprtment, we isolated uterine stromal cells from day4 pregnant mice (n=5 for each genotype), purified total RNA from these cells, pooled these samples and then hybridized to high density affymetrix microarrays. Control vs. KO.
2011-06-03 | E-GEOD-25881 | biostudies-arrayexpress
Project description:Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. Hand2 is involved in coordinating the developmental network of mandibles and the oral apparatus through Hand2-downstream genes and is therefore a major determinant of jaw identity. We used microarrays to detail the global programme of gene expression involved in mandible specification and identified distinct classes of up-regulated genes during this process. Wild-type and Hand2 mutant (Hand2 CAT/+; Wnt1-Cre) embryos were collected at Embryonic day (E) 11.5 or E12.5 for RNA extraction and hybridization on Affymetrix microarrays.
2015-12-15 | E-GEOD-75805 | biostudies-arrayexpress