Transcriptional regulation of postnatal aortic development
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ABSTRACT:
PROVIDER: PRJNA1258874 | ENA |
REPOSITORIES: ENA
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Project description:The aorta exhibits tremendous changes in geometry, composition, and mechanical properties during postnatal development. These changes are necessarily driven by transcriptional changes, both genetically programmed and mechano-responsive, but there has not been a careful comparison of time-course changes in the transcriptional profile and biomechanical phenotype. Here, we show that the greatest period of differential gene expression in the normal postnatal mouse aorta occurs prior to weaning at three weeks of age though with important evolution of many transcripts thereafter. We identify six general temporal patterns, including transcripts that monotonically decrease to lower or increase to higher steady state values as well as those that either peak or dip prior to or near weaning. We show that diverse transcripts within individual groupings correlate well over time, and that sub-sets of these groups correlate well with the developmental progression of different biomechanical metrics that are expected to be involved in mechano-sensing. In particular, expression of genes for elastin and elastin-associated glycoproteins tend to correlate well with the ratio of systolic-to-diastolic stress whereas genes for collagen fibers correlate well with the daily rate of change of systolic stress and genes for mechano-sensing proteins tend to correlate well with the systolic stress itself. We conclude that different groupings of genes having different temporal expression patterns correlate well with different measures of the wall mechanics, hence emphasizing a need for age-dependent, gene-specific computational modeling of postnatal development.
2025-08-04 | GSE296293 | GEO
Project description:Postnatal development of Cardiomyocyte
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Project description:The heterogenity of aortic valve cells present at birth which contruibute to during postnatal maturation is unknown. We utilized single nuclear gene expression profiling to understand the transcritptionally diverse cell type subpopulations present at postnatal day which contribute to postnatal valve maturation.
2025-01-08 | GSE269604 | GEO
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Project description:Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), a post-translational modification critical to stabilizing the collagen triple helix. Quantitative data analysis reported significant regulation of collagen HYP sites across patient categories. Non-collagen type ECM proteins identified (26/44; 59%) have direct interactions in collagen synthesis, regulation, or modification. Network analysis identified BAMBI (BMP and Activin Membrane Bound Inhibitor) as a potential upstream regulator of the collagen interactome. This is the first study to detail the collagen types and HYP modifications associated with human AV development and pCAVS. We anticipate that this study will inform new therapeutic avenues that inhibit valvular degradation in pCAVS and engineered options for valve replacement.
2021-09-09 | PXD021990 | Pride
Project description:During development the fetal heart undergoes a rapid and dramatic transition to adult function through transcriptional and post-transcriptional mechanisms, including alternative splicing (AS). We performed deep RNA-sequencing for high-resolution analysis of transcriptome changes during postnatal mouse heart development using RNA from ventricles and freshly isolated cardiomyocytes (CM) and cardiac fibroblasts (CF). Extensive changes in gene expression and AS occur primarily between postnatal days 1 and 28. CM and CF showed reciprocal regulation of gene expression during postnatal development reflecting differences in proliferative capacity, cell adhesion functions, and mitochondrial metabolism. We found that AS plays a novel role in vesicular trafficking and membrane organization during postnatal CM development. Interestingly, these AS transitions are enriched among targets of two RNA-binding proteins, Celf1 and Mbnl1, which undergo developmentally regulated change in expression. Vesicular traffic genes affected by AS during normal development where Celf1 is down-regulated, showed a reversion to neonatal AS patterns when Celf1 was over-expressed in adults. RNA-seq was performed in RNA samples of ventricles, cardiomyocytes or cardiac fibroblast at different developmental stages; embryonic day 17, postnatal day (PN) 1, 10, 28 and 90 for ventricles, PN1-3, PN28 and PN60 for cardiac fibroblasts, and PN1-2, PN30, and PN67 for cardiomyocytes
2014-04-16 | E-GEOD-49906 | biostudies-arrayexpress
Project description:Role of PARP-1 in transcriptional regulation during development
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Project description:Unraveling the transcriptional regulation of TWIST1 in limb development
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Project description:During development the fetal heart undergoes a rapid and dramatic transition to adult function through transcriptional and post-transcriptional mechanisms, including alternative splicing (AS). We performed deep RNA-sequencing for high-resolution analysis of transcriptome changes during postnatal mouse heart development using RNA from ventricles and freshly isolated cardiomyocytes (CM) and cardiac fibroblasts (CF). Extensive changes in gene expression and AS occur primarily between postnatal days 1 and 28. CM and CF showed reciprocal regulation of gene expression during postnatal development reflecting differences in proliferative capacity, cell adhesion functions, and mitochondrial metabolism. We found that AS plays a novel role in vesicular trafficking and membrane organization during postnatal CM development. Interestingly, these AS transitions are enriched among targets of two RNA-binding proteins, Celf1 and Mbnl1, which undergo developmentally regulated change in expression. Vesicular traffic genes affected by AS during normal development where Celf1 is down-regulated, showed a reversion to neonatal AS patterns when Celf1 was over-expressed in adults.
2014-04-16 | GSE49906 | GEO