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Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction

ABSTRACT: Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction

PROVIDER: PRJNA852184 | ENA |

REPOSITORIES: ENA

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Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction

Project description:Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behaviour of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced coverage by mural cells. Positional transcriptomics reveal that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction.

2023-11-28 | GSE206787 | GEO

Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction.

Project description:Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behavior of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced vascular coverage by mural cells. Positional transcriptomics reveals that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction.

| S-EPMC10739910 | biostudies-literature

Spatiotemporal pattern of the transcriptional regulatory landscape of the mouse ventricle after myocardial infarction

Project description:Spatiotemporal pattern of the transcriptional regulatory landscape of the mouse ventricle after myocardial infarction

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Spatiotemporal transcriptome analysis reveals critical roles for mechano-sensing genes at the border zone in remodeling after myocardial infarction

Project description:The underlying mechanisms of ventricular remodeling after myocardial infarction (MI) remain largely unknown. Here, we performed an integrative analysis of spatial transcriptomics and single-nucleus RNA-seq in a murine MI model and found that mechanical stress-response genes are expressed at the border zone and play a critical role in left ventricular remodeling following MI. An integrative analysis of single-nucleus RNA-seq and spatial transcriptome of the heart tissue after MI identified the unique cluster that appeared at the border zone in an early stage, highly expressing mechano-sensing genes such as Csrp3. AAV9-mediated gene silencing and overexpression of Csrp3 demonstrated that upregulation of Csrp3 plays critical roles in preventing cardiac remodeling after MI via regulation of genes associated with mechano-sensing. Overall, our study not only provides an insight into spatiotemporal molecular changes following MI but also highlights that the mechano-sensing genes at the border zone act as adaptive regulators of left ventricular remodeling.

2022-07-25 | GSE176092 | GEO

Progressive multiple sclerosis

Project description:Progressive multiple sclerosis

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Identifying novel genes related to the peritubular capillary rarefaction in renal interstitial fibrosis through chip sequencing

Project description:Renal interstitial fibrosis (RIF) is the prominent pathological characteristics of deteriorative chronic kidney disease (CKD), leading to peritubular capillary (PTC) rarefaction accompanied by significant hypoxia. However, the underlying mechanisms remain elusive. To deal with this, we constructed the chip sequencing of HK-2 cells in hypoxia to explore critical genes modulated by HIF-1α through peak annotation. Several biomarkers have been identified on the basis of bioinformatics and deserve further research.

2023-11-15 | GSE234719 | GEO

myocardial infarction in Reg3beta knock-out mice

Project description:Affymetrix microarray analysis of molecular changes after myocardial infarction. Samples of heart tissue were analyzed after myocardial infarction from WT and reg3beta knock-out mice. Samples from scar tissue and samples adjacent to the scar were analyzed. In the experiment we primarily compared infarction zone of wild-type to infarction zone of knock-out animals, and remote zone of wild-type to remote zone of knock-outs.

2015-06-29 | E-MTAB-2561 | biostudies-arrayexpress

Sodium accumulation and blood capillary rarefaction in the skin predispose spontaneously hypertensive rats to salt sensitive hypertension.

Project description:We compared tissue Na+ storage in salt sensitive spontaneously hypertensive rats (SHR) versus salt resistant normotensive Brown Norway (BN) rats after salt loading (10 days drinking 1% NaCl solution), the SHR showed significant parallel increase in osmotically inactive Na+ storage in the skin while no significant changes in skin electrolyte concentrations were observed in BN rats. SHR rats after salt treatment exhibited a nonsignificant decrease in skin blood capillary number (rarefaction) while BN rats showed significantly increased skin blood capillary density. Analysis of dermal gene expression profiles in BN rats after salt treatment showed significant up-regulation of genes involved in angiogenesis and proliferation of endothelial cells contrary to the SHR.

2023-01-01 | E-MTAB-11355 | biostudies-arrayexpress

Spatiotemporal transcriptome analysis reveals critical roles for mechano-sensing genes at the border zone in remodeling after myocardial infarction

Project description:Spatiotemporal transcriptome analysis reveals critical roles for mechano-sensing genes at the border zone in remodeling after myocardial infarction

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Identification of altered cell signaling pathways in stable and progressive chronic lymphocytic leukemia

Project description:Chronic lymphocytic leukemia (CLL) is characterized by significant biological and clinical heterogeneity. This study was designed to explore CLL B-cells’ proteomic profile in order to identify biological processes affected at an early stage and during disease evolution as stable or progressive. Purified B cells from 11 untreated CLL patients were tested at two time points by liquid chromatography-tandem mass spectrometry. Patients included in the study evolved to either progressive (n=6) or stable disease (n=5). First, at an early stage of the disease (Binet stage A), based on the relative abundance levels of 389 differentially expressed proteins (DEP), samples were separated into stable and progressive clusters with the main differentiating factor being RNA splicing pathway. Next, in order to test how the DEPs affect RNA splicing, a RNA-Seq study was conducted for 4 Stable and 4 Progressive CLL patients, showing 4217 differentially spliced genes between the two clusters. Distinct longitudinal evolutions were observed with predominantly proteomic modifications in the stable CLL group and spliced genes in the progressive CLL group. Splicing events were shown to be 6 times more frequent in the progressive CLL group. The main aberrant biological processes controlled by DEP and spliced genes in the progressive group were cytoskeletal organization, Wnt/β-catenin signaling, mitochondrial and inositol phosphate metabolism with a downstream impact on CLL B-cell survival and migration. This study suggests that proteomic profiles at the early stage of CLL can discriminate progressive from stable disease and that RNA splicing dysregulation underlies CLL evolution, which opens new perspectives in terms of biomarkers and therapy.

2021-06-05 | GSE176141 | GEO

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