Similar Datasets
Project description:Shroom3-Fyn interaction determines nephrin phosphorylation and Albuminuria in allografts
| PRJNA432731 | ENA
Project description: Not available
| S-EPMC6218856 | biostudies-literature
Project description:This RNA-sequencing study investigates the role of SHROOM3 in podocyte function and its contribution to renal pathophysiology. Podocytes are highly specialized epithelial cells critical for glomerular filtration barrier integrity. The study explores how SHROOM3 deficiency affects podocyte cytoskeletal architecture and focal adhesion dynamics in the context of Adriamycin-induced nephropathy, a widely used experimental model of podocyte injury and proteinuric kidney disease. We performed transcriptome analysis using RNA-sequencing on human podocyte cell lines, comparing Control (n=4) and SHROOM3 knockdown (KD) podocytes (n=4). Our objective was to identify the molecular mechanisms and signaling pathways through which SHROOM3 regulates podocyte cytoskeletal organization, with particular focus on stress fiber formation and focal adhesion assembly/disassembly. The dataset provides comprehensive gene expression profiles revealing how SHROOM3 deficiency exacerbates podocyte injury, disrupts actin cytoskeleton dynamics, and impairs focal adhesion stability during nephropathy progression.
2025-04-17 | GSE294734 | GEO
Project description:The loss of SHROOM3 plays an important role at the neuroepithelial stage, demonstrating the indispensability of SHROOM3 and indicating the great potential of organoids in understanding the mechanism of neural tube defects (NTDs).
2025-11-01 | GSE217791 | GEO
Project description:We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays. Immunohistochemistry for C4d was performed on paraffin-embedded sections. Of the 255 biopsies analyzed, 51% were C4d negative, 4% were minimal, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+. Minimal and focal/ diffuse PTC C4d+ staining were associated with a higher frequency of donor-specific anti-HLA antibodies (DSA) (67% vs. 82% vs. 25%), antibody mediated rejection (AMR) (66% vs. 89% vs. 19%) and mean glomerulitis (0.88 vs. 0.65 vs. 0.25, p=0.003), interstitial inflammation (1.25 vs. 1.41 vs. 0.79; p=0.003) and peritubular capillaritis scores (1.5 vs. 1.5 vs. 0.34; p < 0.001), compared to the C4d negative group, respectively. There were no differences in the DSA frequency, AMR rate, and Banff scores between isolated glomerular C4d+ and negative patients. While both minimal and focal/diffuse C4d+ biopsies showed increased expression of genes related to the immune response, and interferon-gamma and rejection induced, cytotoxic T cell and constitutive macrophage-associated pathogenesis based transcripts, there was no activation of immune-response related genes in isolated glomerular C4d+ biopsies. In summary, minimal PTC C4d+ staining but not isolated glomerular C4d+ staining is associated with AMR.
2012-05-29 | GSE38262 | GEO
Project description:We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays. Immunohistochemistry for C4d was performed on paraffin-embedded sections. Of the 255 biopsies analyzed, 51% were C4d negative, 4% were minimal, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+. Minimal and focal/ diffuse PTC C4d+ staining were associated with a higher frequency of donor-specific anti-HLA antibodies (DSA) (67% vs. 82% vs. 25%), antibody mediated rejection (AMR) (66% vs. 89% vs. 19%) and mean glomerulitis (0.88 vs. 0.65 vs. 0.25, p=0.003), interstitial inflammation (1.25 vs. 1.41 vs. 0.79; p=0.003) and peritubular capillaritis scores (1.5 vs. 1.5 vs. 0.34; p < 0.001), compared to the C4d negative group, respectively. There were no differences in the DSA frequency, AMR rate, and Banff scores between isolated glomerular C4d+ and negative patients. While both minimal and focal/diffuse C4d+ biopsies showed increased expression of genes related to the immune response, and interferon-gamma and rejection induced, cytotoxic T cell and constitutive macrophage-associated pathogenesis based transcripts, there was no activation of immune-response related genes in isolated glomerular C4d+ biopsies. In summary, minimal PTC C4d+ staining but not isolated glomerular C4d+ staining is associated with AMR. Total of 92 arrays included in this study. G1. Native pre-implantation biopsies (N= 10); G2. Focal or diffuse PTC C4d+ (N= 13); G3. Minimal PTC C4d+ (N=4); G4. Isolated glomerular C4d+ with glomerular disease (N= 13); G5. Isolated glomerular C4d+ staining without glomerular disease (N= 15); G6. C4d negative with glomerular disease (N= 12); G7. C4d negative biopsies without evidence of glomerular disease (N=25)
2012-05-28 | E-GEOD-38262 | biostudies-arrayexpress
Project description:Cardiomyocyte (CM) polyploidization has been associated with cardiac injury responses, including regeneration and heart failure. However, our understanding of the comprehensive mechanisms governing CM ploidy and its influence on heart physiology has been hindered by a lack of experimental tools. To address this issue and uncover novel genetic regulators, we surveyed CM ploidy across a new genetic resource known as the Hybrid Rat Diversity Panel and find significant variation in ploidy phenotypes across the panel. Using select rat strains with divergent displays of CM ploidy, we found that hyperpolyploidization (≥8N) positively correlates with various physiological parameters namely left ventricular dilation and reduced ejection fraction. Genome-wide association mapping identifies several loci significantly associated with frequency of hyperpolyploid CMs. Investigation of genes harboring damaging protein coding variants identified enrichment of cytoarchitectural genes, of which the ACTIN-binding protein, Shroom3, was found to be strongly and specifically expressed in CMs and harbor 7 damaging protein coding variants. Indeed, CM-specific deletion of Shroom3 increased hyperpolyploidization in adult mice, while also promoting left ventricular dilation and reducing cardiac function. Furthermore, functional characterization of single nucleotide variants resulting in amino acid changes within SHROOM3 confirmed two protein coding variants that disrupted SHROOM3-ACTIN interaction. This study elucidates the genetic determinants of CM ploidy phenotypes and solidifies a relationship between CM ploidy and left ventricular function. Importantly, CM intrinsic expression of at least one gene mapped in this study, Shroom3, is confirmed to regulate CM hyperpolyploidization and cardiac function.
2026-03-25 | GSE307551 | GEO
Project description:Cardiomyocyte (CM) polyploidy is widely observed across the animal kingdom and various ploidy states are associated with cardiac injury responses, including regeneration and heart failure. However, our understanding of the comprehensive mechanisms governing CM ploidy and its relationship with heart physiology has been hindered by a lack of experimental tools. To address this issue and uncover novel genetic regulators, we surveyed CM ploidy across a new genetic resource known as the Hybrid Rat Diversity Panel and founnd significant variation in ploidy phenotypes across the panel. Using select rat strains with divergent displays of CM ploidy, we found that hyperpolyploidization (≥8N) positively correlates with various physiological parameters namely left ventricular dilation and reduced ejection fraction. Genome-wide association mapping identified several loci significantly associated with frequency of hyperpolyploid CMs. Investigation of genes harboring damaging protein coding variants within these loci identified enrichment of cytoarchitectural genes, of which the ACTIN-binding protein, Shroom3, was found to be strongly and specifically expressed in CMs and harbors 7 damaging protein coding variants. CM-specific deletion of Shroom3 resulted in increased hyperpolyploidization and promoted left ventricular dilation and reduced ejection fraction. Furthermore, functional characterization of single nucleotide variants resulting in amino acid changes within SHROOM3 confirmed two protein coding variants that disrupted SHROOM3-ACTIN interaction and led to altered expression of cell cycle genes. This study elucidates the genetic determinants of CM ploidy phenotypes and solidifies a correlative relationship between CM ploidy and left ventricular function. Importantly, CM intrinsic expression of at least one gene mapped in this study, Shroom3, is confirmed to regulate CM hyperpolyploidization and cardiac function.
2026-03-25 | GSE314057 | GEO
Project description: Not available
| S-EPMC4382250 | biostudies-literature
Project description:Rapidly progressive glomerulonephritis (RPGN) is the most aggressive group of autoimmune kidney disease with the worst prognosis. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, anti-glomerular basement membrane (anti-GBM) and lupus nephritis are the most common causes of RPGN and are characterized by the formation of glomerular crescents and infiltration of leukocytes that eventually lead to glomerulosclerosis and kidney failure. In this work, we used high-resolution spatial transcriptomics of 32 ANCA, 19 lupus nephritis, 6 anti-GBM, and 6 control patients to understand how intercellular signaling between immune and renal tissue cells leads to renal inflammation and glomerular injury. Using 3,218,210 immune and kidney cells, we observed that the biological pathways involved in the sequence of glomerular crescent formation are similar across the diseases. While innate immune cells infiltrated the glomerular compartment relatively early, later increases in adaptive immune cells were largely restricted to the periglomerular regions. These changes in immune cells temporally correlated with increases in glomerular parietal epithelial (PEC) and fibrotic mesangial cells, suggesting disease-relevant functional signaling between these immune and renal cells. Cell communication analysis revealed early disease PDGF signaling from epithelial and mesangial cells to PECs, causing their activation and proliferation. At later stages, TGF-β signaling from macrophages, T cells, epithelial cells, and mesangial cells to PECs triggered the expression of extracellular matrix components resulting in glomerulosclerosis. Our results highlight a spatio-temporally conserved progression into glomerular crescents and sclerosis for ANCA, lupus nephritis, and anti-GBM disease, which is driven by consecutive PDGF and TGF-β signaling to PECs.
2025-08-19 | GSE303481 | GEO