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Temporal and functional determinants of intra-hepatic vascular homeostatic specialization [mouse liver]

ABSTRACT: Temporal and functional determinants of intra-hepatic vascular homeostatic specialization [mouse liver]

PROVIDER: PRJNA727692 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14275784_1.fastq.gz	Fastqsanger.gz
	SRR14275784_2.fastq.gz	Fastqsanger.gz
	SRR14275785_1.fastq.gz	Fastqsanger.gz
	SRR14275785_2.fastq.gz	Fastqsanger.gz
	SRR14275786_1.fastq.gz	Fastqsanger.gz

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Temporal and functional determinants of intra-hepatic vascular homeostatic specialization

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Temporal and functional determinants of intra-hepatic vascular homeostatic specialization [human liver + HUVEC]

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Temporal and functional determinants of intra-hepatic vascular homeostatic specialization

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2022-04-01 | GSE172362 | GEO

Temporal and functional determinants of intra-hepatic vascular homeostatic specialization [mouse liver]

Project description:Comparison of isolated mouse liver endothelial cells from Control and c-Maf endothelial deficient mice at 8 weeks of age.

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Temporal and functional determinants of intra-hepatic vascular homeostatic specialization [human liver + HUVEC]

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Molecular determinants of nephron vascular specialization in the kidney

Project description:Molecular determinants of nephron vascular specialization in the kidney

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Molecular determinants of nephron vascular specialization in the kidney

Project description:The kidney vasculature is specialized to filter waste products from the blood, regulate blood pressure, and balance electrolytes. Although recent advances in stem cell studies have enabled the partial generation of kidney tissues in vitro, recapitulating the complex vascular structures of the kidney remains a daunting task. The molecular pathways that specify and sustain kidney vascular heterogeneity to perform these diverse tasks are not well characterized. Here, we have employed high throughput bulk and single-cell RNA sequencing of the non-lymphatic vasculature of the kidney to uncover the progression of pathways that dictate the developmental transition of nephrogenesis and vascular zonation from embryos to adulthood. We show that glomeruli and its associated vessels, manifest vascular-specific signatures expressing defined transcription factors, ion channels, solute transporters, and paracrine factors choreographing kidney functions. Notably, the ontology of the glomerulus coincides with induction of several unique transcription factors, including Tbx3, Gata5, Prdm1, and Pbx1. Selective deletion of Tbx3 in endothelial cells result in glomerular hypoplasia, microaneurysms and regressed fenestrations leading to fibrosis. Unraveling the molecular determinants of kidney vascular signatures will lay the foundation for rebuilding nephrons and understanding the pathogenesis of kidney diseases.

2019-09-20 | GSE137786 | GEO

Molecular determinants of nephron vascular specialization in the kidney.

Project description:Although kidney parenchymal tissue can be generated in vitro, reconstructing the complex vasculature of the kidney remains a daunting task. The molecular pathways that specify and sustain functional, phenotypic and structural heterogeneity of the kidney vasculature are unknown. Here, we employ high-throughput bulk and single-cell RNA sequencing of the non-lymphatic endothelial cells (ECs) of the kidney to identify the molecular pathways that dictate vascular zonation from embryos to adulthood. We show that the kidney manifests vascular-specific signatures expressing defined transcription factors, ion channels, solute transporters, and angiocrine factors choreographing kidney functions. Notably, the ontology of the glomerulus coincides with induction of unique transcription factors, including Tbx3, Gata5, Prdm1, and Pbx1. Deletion of Tbx3 in ECs results in glomerular hypoplasia, microaneurysms and regressed fenestrations leading to fibrosis in subsets of glomeruli. Deciphering the molecular determinants of kidney vascular signatures lays the foundation for rebuilding nephrons and uncovering the pathogenesis of kidney disorders.

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Subsoil specialization

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Dissecting the sequence and structural determinants guiding m6A deposition and evolution via inter- and intra-species hybrids

Project description:N6-methyladenosine (m6A) is the most abundant mRNA modification, primarily implicated in controlling mRNA stability. The distribution of m6A varies considerably between and within species, and genetic variants associated with differences in m6A levels between humans have been associated with disease. Yet, the determinants governing m6A variability are poorly understood: It is unclear whether it is driven by changes in genetic sequences (‘cis’) or cellular environments (‘trans’) and what its underlying mechanisms are. Here we dissect these determinants via interspecies hybrids in yeast and mammalian systems, allowing us to interrogate methylation at two distinguishable alleles in a shared environment. We find that m6A evolution is driven primarily in ‘cis’, and identify two mechanisms driving m6A changes: (1) Sequence variations leading to formation/disruption of m6A consensus motifs, and (2) Changes in local mRNA secondary structure, whereby RNA structuredness inhibits m6A formation. We demonstrate that secondary structure is causal, and that gain and loss of structure - even when driven by mutations distant from the modified position - are sufficient to abolish and acquire methylation, respectively. Using intra-species hybrids, massively parallel reporter assays and reanalyzing m6A-QTLs among 60 human individuals, we reveal the combined role of sequence and structure in shaping variability in m6A levels also across individuals from the same species. Finally, we demonstrate that differences in m6A levels between homologous genes lead to allele-specific changes in gene expression. Our findings thus define the determinants governing m6A evolution and diversity and characterize the consequences thereof on gene expression regulation.

2024-01-24 | GSE232450 | GEO

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