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Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation

ABSTRACT: Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation

PROVIDER: PRJNA657814 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12466259.fastq.gz	Fastqsanger.gz
	SRR12466260.fastq.gz	Fastqsanger.gz
	SRR12466261.fastq.gz	Fastqsanger.gz
	SRR12466262.fastq.gz	Fastqsanger.gz
	SRR12466263.fastq.gz	Fastqsanger.gz

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Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation

Project description:Hand1 and Hand2 are transcriptional factors, and knockout mice of these genes show left and right ventricular hypoplasia, respectively. However, their function and expression in human cardiogenesis are not well studied. To delineate their expressions and assess their functions in human cardiomyocytes (CMs) in vitro, we established two triple reporter human induced pluripotent stem cell lines, HAND1mCherry, HAND2EGFP, with MYH6-driven iRFP670 or constitutive tagBFP expression and investigated their expression dynamics during cardiac differentiation. On day 5 of the differentiation, HAND1 expression marked cardiac progenitor cells. We profiled the CM subpopulations on day 20 with RNA-sequencing and found that mCherry+ CMs showed higher proliferative ability than mCherry- CMs and identified CD105 as a surface marker of highly proliferative CMs. Finally, we revealed that LEF1 is a key regulator of proliferation and is repressively regulated by HAND1 and HAND2.

2021-07-22 | GSE156394 | GEO

Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation.

Project description:Hand1 and Hand2 are transcriptional factors, and knockout mice of these genes show left and right ventricular hypoplasia, respectively. However, their function and expression in human cardiogenesis are not well studied. To delineate their expressions and assess their functions in human cardiomyocytes (CMs) in vitro, we established two triple-reporter human induced pluripotent stem cell lines that express HAND1mCherry, HAND2EGFP and either MYH6-driven iRFP670 or tagBFP constitutively and investigated their expression dynamics during cardiac differentiation. On day 5 of the differentiation, HAND1 expression marked cardiac progenitor cells. We profiled the CM subpopulations on day 20 with RNA sequencing and found that mCherry+ CMs showed higher proliferative ability than mCherry- CMs and identified a gene network of LEF1, HAND1, and HAND2 to regulate proliferation in CMs. Finally, we identified CD105 as a surface marker of highly proliferative CMs.

| S-EPMC8365100 | biostudies-literature

Co-effects of m6A dynamics and chromatin accessibility changes regulate cardiomyocyte differentiation

Project description:The growth and differentiation of cardiomyocytes are primarily driven by gene expression dynamics, with various epigenetic modifications playing a crucial role in this process. One of the most common modifications on mRNA, m6A, influences the regulation of mRNA metabolism; however, its function remains enigmatic. In this study, we identified a correlation between m6A modification and cardiomyocyte differentiation by profiling m6A dynamics during the transition of pluripotent stem cells into cardiomyocytes. Although the overall m6A modification level remains relatively stable, most genes exhibit changes in their m6A levels as cardiomyocyte differentiation progresses. We observed that alterations in chromatin accessibility can impact the binding capabilities of m6A writers, erasers, and readers, consequently affecting m6A levels. Furthermore, the coordinated changes of m6A and chromatin accessibility are closely associated with early-stage cardiomyocyte differentiation. These findings suggest that m6A is a significant factor in determining the fate of cardiomyocyte differentiation, shedding light on its role in this critical process.

2023-08-24 | GSE231549 | GEO

HAND1 ChIP-seq at day 3 of cardiac differentiation from human embryonic stem cells

Project description:The aim was to identify HAND1 binding sites at low and high HAND1 levels at an early stage of hESC cardiac differentiation. We generated a HAND1-AM-Tag (Active Motif) knock-in to enable sensitive and specific ChIP-seq analysis. The hESCs were differentiated in 3D embryoid bodies with BMP4, Activin A and CHIR. To increase HAND1 levels, we treated one population with SB431542 from day 2. Samples were harvested on day 3 for ChIP.

2025-02-13 | E-MTAB-14280 | biostudies-arrayexpress

Adgrg1 is a New Transcriptional Target of Hand1 During Trophoblast Giant Cell Differentiation

Project description:The placenta, forming the maternal–fetal interface, is essential for the survival and development of the fetus. It has been shown that the basic helix-loop-helix (bHLH) transcription factor Hand1 plays an important role in trophoblast giant cells (TGCs) differentiation during placental development in mice. However, the underlying molecular mechanism remains elusive. We hereby report that Adgrg1 (GPR56), a G protein coupled receptor, was a new transcriptional target of Hand1. Hand1 activated the expression of Adgrg1 by binding to its promoter region during TGCs differentiation. Double in situ hybridization revealed co-expression of Hand1 and Adgrg1 in TGCs, and Adgrg1 was located to Prl2c2+ TGCs in the junctional zone of the placenta. Knockdown of Adgrg1 not only led to increased expression of Prl2c2, but also the improvement of cell migration during TGC differentiation. Moreover, the ligands of Adgrg1, Tgm2 and Col3a1, were expressed in Prl2c2+ TGCs located in the placental junctional zone and maternal spiral arteries, respectively, further providing preconditions for the function of Adgrg1 in TGCs. Collectively, these results demonstrate that Adgrg1 is a new transcriptional target of Hand1, affecting Prl2c2 expression and cell migration during TGCs differentiation. Tgm2 and Col3a1 may be involved in TGC differentiation regulated by Adgrg1 in the manners of autocrine or paracrine. As a transmembrane receptor, Adgrg1 perhaps could act as a potential therapeutic target for placental-associated diseases caused by abnormal trophoblast migration, providing new insights for the preventions and therapies of placenta-related diseases.

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Single cell RNA-seq to resolve heterogeneity in a cardiac differentiation timecourse from wild-type and HAND1-null hESCs

Project description:The aim was to assess the role of HAND1 in cardiac differentiation. The differentiation protocol was designed to promote cell diversity. For wild-type and HAND1-null cell lines we combined cells differentiating under different conditions: 50% control, 25% SB-treated (day 2-3) and 25% DMH1-treated (day 2-3). The addition of SB at day 2, inhibited SMAD2/3 phosphorylation and created a high BMP signalling bias to restrict cardiac differentiation in favour of other mesodermal lineages, whereas the addition of DMH1 at day 2, inhibited SMAD1/5/8 phosphorylation to create a high Activin signaling bias to promote the co-differentiation of endoderm. Samples were collected at days 3, 4, 5, 6, 7, 8 and 10 for wild-type and HAND1-null populations. An additional day 7 and 8 sample was included for the wild-type, which was generated in the same condition.

2025-02-13 | E-MTAB-14285 | biostudies-arrayexpress

HAND1 knockdown disrupts trophoblast gene expression in vitro in Bewo cells

Project description:Congenital heart disease (CHD) affects nearly 1% of births annually, and neonatal and perinatal outcomes in cases of CHD are strongly impacted by pregnancy outcomes. CHD pregnancies carry increased risk of developing pathologies of abnormal placentation including fetal growth restriction, preeclampsia, preterm birth, and stillbirth. HAND1 is a gene associated with CHD. In this study, we aimed characterize the mechanistic impacts of disrupting HAND1 on human placenta trophoblast cell lines.

2022-08-02 | GSE209620 | GEO

HAND1 knockdown disrupts trophoblast gene expression in vitro- human vascular endothelial cell

2022-08-03 | GSE210318 | GEO

Co-effects of m6A dynamics and chromatin accessibility changes regulate cardiomyocyte differentiation

Project description:Co-effects of m6A dynamics and chromatin accessibility changes regulate cardiomyocyte differentiation

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RNA-seq of sorted cells at day 3 of cardiac differentiation based on HAND1 level

Project description:The aim of the experiment was to identify HAND1 target genes and its impact on chromatin accessibility in relation to cardiac development. A HAND1-null hESC line was used, in which a doxycycline-inducible HAND1-T2A-BFP transgene had been integrated in approximately half of the cells for HAND1 rescue / overexpression. The hESCs were differentiated with BMP4, Activin A and CHIR. On day 2.5, doxycycline was added. On day 3, cells were dissociated and sorted by BFP level using FACS. Samples were immediately processed for RNA-seq and ATAC-seq.

2025-02-13 | E-MTAB-14278 | biostudies-arrayexpress

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