Integrin b1 acetylation-induced transcriptomic reprograming of mouse embryonic endothelial cells and functions
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA997375 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Reciprocal regulation of integrin-dependent cell-matrix adhesions and cell-cell junctions is critical for controlling endothelial permeability and proliferation in cancer and inflammatory diseases, but remain poorly understood. Here, we investigated how acetylation of the distal NPKY-motif of b1-integrin influences endothelial cell physiology and barrier function. Expression of an acetylation-mimetic B1A-K794Q-GFP mutant induced transcriptomic reprograming of embryonic endothelial cells particularly in genes responsible for cell adhesion, proliferation, polarity and barrier function. B1A-K794Q-GFP induced a constitutive activation of MAPK signaling, an impairment of junctions, increased proliferation and an altered contact inhibition at confluency. Structural analysis of integrin b1 interaction with KINDLIN-2, biochemical pulldown assay and molecular dynamic analysis showed that acetylation of K794 increases KINDLIN-2 binding to the integrin b1 cytoplasmic tail. Accordingly, altering KINDLIN-2 levels modified Claudin-5 expression and endothelial barrier function. Revealing how integrin b1 acetylation regulates endothelial cell junctions offers new therapeutic possibilities for controlling vascular permeability.
2024-01-01 | GSE238019 | GEO
Project description:Integrins are extracellular matrix receptors comprised of an a and b subunit that connect and mediate signaling between cells and the surrounding matrix. In organogenesis of epithelial tissues, the b1 integrin subunit regulates essential epithelial cell functions, but the role of b1 integrin in epithelial repair is poorly understood. To define the role of b1 integrin during alveolar repair, we challenged b1 integrin deficient mice with intratracheal lipopolysaccharide, resulting in increased mortality with emphysematous lungs 21 days following injury. The alveolar barrier was repopulated with an overabundance of type 2 alveolar epithelial cells, with reduced numbers of elongated alveolar type 1 cells, suggesting b1 integrin is required for type 2 to type 1 epithelial transition. Consistent with this finding, b1 deficient type 2 epithelial cells proliferated at increased rates throughout repair, lacked actin-rich cellular protrusions necessary for lateral cellular extension, and exhibited transcriptomic dysregulation of adherens junction and actin polymerization pathways. Finally, we show that b1 integrin balances actin polymerization versus stabilization through GTPase activation. Taken together, these data support a novel role for b1 integrin in re-establishing the alveolar niche after injury through modulation of type 2 epithelial cell proliferation and cytoskeletal-dependent cell shape change.
2023-06-10 | GSE205882 | GEO
Project description:Integrin b1-deficient mice have a defect in the differentiation of MZ B cells and plasma cells.We performed a genome-wide transcriptome analysis of ex vivo-sorted Fo B, transitional B and MZ B cells of in Integrin b1 KO and Integrin b1 WT mice. We also performed invitro culture of CD93+ (AA4.1+) transitional B cells to study the role of PI3 Kinase signalling.
2022-09-19 | GSE213512 | GEO
Project description:In this study, we investigated the function of beta integrins in developing islet beta-cells by targeting the deletion of exon 3 of the B1 integrin gene using a Cre-lox approach. Our results demonstrate that this class of integrin receptors is critically important for proper beta cell expansion during development
2013-07-31 | E-MEXP-3736 | biostudies-arrayexpress
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation. To investigate the mechanisms responsible for the abnormalities in b1 integrin mutant mice, we performed mRNA expression microarray analyses of E12.5 wild-type and mutant hearts, well before any obvious dysfunction. RNA was isolated from wild-type and mutant hearts, and arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates of WT and KO mouse hearts.
2009-01-14 | E-GEOD-14411 | biostudies-arrayexpress
Project description:Integrins, the principal extracellular matrix (ECM) receptors of the cell, promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that integrin b1, a highly expressed subunit in lung epithelium, is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin b1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin b1-mediated adhesion to ECM but are dependent on integrin b1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). Together, these studies support a critical role for integrin b1 in lung tumorigenesis that is mediated through constitutive, ECM-binding independent signaling involving the cytoplasmic tail.
2022-08-01 | GSE175687 | GEO
Project description:b1-integrin regulates marginal zone B cell differentiation
| PRJNA881272 | ENA
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation.
2009-01-15 | GSE14411 | GEO
Project description:Fibrosis, characterized by sustained activation of myofibroblasts and excessive extracellular matrix (ECM) deposition, is known to be associated with chronic inflammation. RIPK3, a key kinase mediating TNF-driven necroptosis signaling, is upregulated in fibrosis and contributes to the TNF-mediated inflammation. In biliary duct ligation-induced liver fibrosis, we found that myofibroblasts are the major cell type expressing RIPK3. Genetic ablation of b1 integrins, the major profibrotic ECM receptors in fibroblasts, not only abolished ECM fibrillogenesis but also blunted RIPK3 expression via an epigenetic mechanism mediated by the chromatin remodeling factor CHD4. While the function of CHD4 has been conventionally linked to NuRD and ChAHP complexes, we found that CHD4 potently repressed a set of genes, including Ripk3, with high locus specificity but independent of either the NuRD or ChAHP complex. Thus, our data uncover that b1 integrin intrinsically links fibrotic signaling to RIPK3-driven inflammation via a novel mode of action of CHD4.
2023-10-23 | GSE229795 | GEO
Project description:Emerging evidence points to post translational modification (PTM) of nuclear lamins as a key regulator of their diverse roles in nuclear organization, chromatin stability, DNA repair, and cell cycle progression. However, the functions of many of these PTMs remain uncharacterized. Here, we demonstrate a role for acetylation at lysine 134 on lamin B1 in slowing the G1 to S cell cycle transition by inhibiting resolution of DNA damage by canonical nonhomologous end joining.
2021-01-08 | PXD022974 | Pride