Human model of IRX5 mutations reveals key role for this transcription factor in ventricular conduction
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB39654 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4393230.fastq.gz | Fastqsanger.gz | |||
| ERR4393240.fastq.gz | Fastqsanger.gz | |||
| ERR4393250.fastq.gz | Fastqsanger.gz | |||
| ERR4393260.fastq.gz | Fastqsanger.gz | |||
| ERR4393231.fastq.gz | Fastqsanger.gz |
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Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
2023-04-05 | GSE202583 | GEO
Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
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Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
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Project description:In this study, we aimed to differentiate atrioventricular (AV) canal-like cardiomyocytes (AVCM) from hiPSCs to facilitate the study of disorders that affect the AV conduction axis. hiPSC-derived AVCM preferentially expressed AV canal-associated genes MSX2, TBX2 and TBX3. Single cell RNA sequencing and comparative analysis with mouse heart further validated their AV canal-like identity. In addition, hiPSC-AVCM demonstrated sensitivity to ivabradine and carbachol, indicating the presence of key nodal currents If and IKACh. To model the AV conduction axis, we created an organoid-based tissue model. These so-called “assembloids” consisted of atrial, AVC, and ventricular organoids, which exhibited spontaneous contractions and unidirectional conduction with impulses initiated predominantly at the atrial end. Remarkably, we observed slower conduction in the AVC region of the assembloid, effectively recapitulating the “fast-slow-fast” conduction pattern found in the early heart tube. Our results demonstrate that hiPSC-derived AVCM recapitulate molecular and electrophysiological properties of in vivo AV canal cardiomyocytes and tissue models incorporating this cell type enhance our ability to evaluate complex cardiac conduction disorders.
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Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
2022-11-01 | GSE202085 | GEO
Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
2022-11-01 | GSE202086 | GEO
Project description:Analysis of the roles of Irx3 and Irx5 transcription factors in mouse heart development and postnatal heart function. Results show that show that Irx3 and Irx5 have redundant function in the in the endocardium to regulate atrioventricular canal morphogenesis and outflow tract formation. A postnatal deletion of Irx3 and Irx5 surprisingly results in a restoration of the repolarization gradient that is altered in Irx5 mutant hearts, suggesting a model whereby postnatal Irx3 activity is normally repressed by Irx5. 4 genotypes were analyzed: Irx5+/- (3 samples), Irx3-/-;Irx5+/- (4 samples), Irx5-/- (3 samples), Irx5-/-;Irx3-/- (4 samples). The Irx5+/- samples are the reference.
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Project description:Neural Cell Adhesion Molecule (NCAM-1) is Required for Ventricular Conduction System Development
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