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Single cell transcriptomic analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator.

ABSTRACT: Single cell transcriptomic analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator.

PROVIDER: PRJNA1029000 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26410269.fastq.gz	Fastqsanger.gz
	SRR26410270.fastq.gz	Fastqsanger.gz
	SRR26410271.fastq.gz	Fastqsanger.gz
	SRR26410272.fastq.gz	Fastqsanger.gz

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Similar Datasets

Single cell transcriptomic analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator.

Project description:The management of preretinal fibrovascular membranes, a devastating complication of advanced diabetic retinopathy (DR), remains challenging. We characterized the molecular profile of cell populations in these fibrovascular membranes to identify new therapeutic targets. Preretinal fibrovascular membranes were surgically removed from patients and submitted for single cell RNA (scRNA) sequencing. Differential gene expression was implemented to define the transcriptomic profile of these cells and revealed the presence of endothelial, inflammatory, and stromal cells. Endothelial cell re-clustering identified subclusters characterized by non-canonical trascriptomic profile, and active angiogenesis. Deeper investigation of the inflammatory cells showed a subcluster of macrophages expressing pro-angiogenic cytokines, presumably contributing to angiogenesis. The stromal cell cluster included a pericyte-myofibroblast transdifferentiating subcluster, indicating the involvement of pericytes in fibrogenesis. Differentially expressed gene analysis showed that Adipocyte Enhancer-binding Protein 1, AEBP1, was significantly upregulated in myofibroblast clusters, suggesting that this molecule may have a potential role in transformation. Cell culture experiments with human retinal pericytes (HRP) in high glucose condition confirmed the molecular transformation of pericytes towards myofibroblastic lineage. siAEBP1 transfection in HRP reduced the expression of profibrotic markers in high glucose. In conclusion, AEBP1 signaling modulates pericyte-myofibroblast transformation, suggesting that targeting AEBP1 could prevent scar tissue formation in advanced DR.

2023-11-02 | GSE245561 | GEO

Single-cell transcriptomics analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator.

Project description:The management of preretinal fibrovascular membranes, a devastating complication of advanced diabetic retinopathy (DR), remains challenging. We characterized the molecular profile of cell populations in these fibrovascular membranes to identify potentially new therapeutic targets. Preretinal fibrovascular membranes were surgically removed from patients and submitted for single-cell RNA-Seq (scRNA-Seq). Differential gene expression was implemented to define the transcriptomics profile of these cells and revealed the presence of endothelial, inflammatory, and stromal cells. Endothelial cell reclustering identified subclusters characterized by noncanonical transcriptomics profile and active angiogenesis. Deeper investigation of the inflammatory cells showed a subcluster of macrophages expressing proangiogenic cytokines, presumably contributing to angiogenesis. The stromal cell cluster included a pericyte-myofibroblast transdifferentiating subcluster, indicating the involvement of pericytes in fibrogenesis. Differentially expressed gene analysis showed that Adipocyte Enhancer-binding Protein 1, AEBP1, was significantly upregulated in myofibroblast clusters, suggesting that this molecule may have a role in transformation. Cell culture experiments with human retinal pericytes (HRP) in high-glucose condition confirmed the molecular transformation of pericytes toward myofibroblastic lineage. AEBP1 siRNA transfection in HRP reduced the expression of profibrotic markers in high glucose. In conclusion, AEBP1 signaling modulates pericyte-myofibroblast transformation, suggesting that targeting AEBP1 could prevent scar tissue formation in advanced DR.

| S-EPMC10896003 | biostudies-literature

Silencing of AEBP1 in U87MG glial cells and Chip-chIP with AEBP1 antibody

Project description:AEBP1 has been identified as a transcriptional repressor playing a significant role in adipogenesis. Recently, we have found that AEBP1 is specifically upregulated in primary glioblastoma. We have used gene silencing to identify genes perturbed upon AEBP1 downregulation and ChIP-chip technique to identify its genomic targets of binding and regulation to understand the un-annotated/undescribed role of this transcription factor in gliomagenesis. Cells either mock silenced or silenced using siRNA against AEBP1 were harvested at 46hrs post transfection. Gene expression was profiled for control and AEBP1 silenced cells. comparison of AEBP1/Rabbit IgG/ Glial cells

2012-04-29 | E-GEOD-18892 | biostudies-arrayexpress

Silencing of AEBP1 in U87MG glial cells and Chip-chIP with AEBP1 antibody

2012-04-30 | GSE18892 | GEO

Effects of AEBP1 knockdown on gene expression profiles in HUVEC

Project description:We identified adipocyte enhancer binding protein 1 (AEBP1) as a novel tumor endothelial marker in colorectal cancer (CRC). To identify target genes of AEBP1 in endothelial cells, we knocked down AEBP1 in human umbilical vein endothelial cells (HUVECs). We found that genes associated with angiogenesis including aquaporin 1 (AQP1) and periostin (POSTN) are downregulated by AEBP1 knockdown in HUVECs, suggesting that AEBP1 may promote tumor angiogenesis through regulating these genes.

2020-04-01 | GSE138427 | GEO

Role of AEBP1 in LX-2 cells

Project description:To investigate the role of AEBP1 involved in hepatic stellate cells (HSCs), we inhibited AEBP1 expression by specific siRNA in human HSC line LX-2 cells. Total RNA was loaded for bulk RNA sequencing.

2023-10-19 | GSE219170 | GEO

Identification of AEBP1-binding proteins

Project description:Identification of AEBP1-binding proteins, gel-based proteomics

2025-08-15 | PXD067349 | Pride

Effects of AEBP1 knockdown on gene expression profiles in cancer-associated fibroblasts

Project description:We identified adipocyte enhancer binding protein 1 (AEBP1) as a novel cancer-associated fibroblast (CAF) marker in oral squamous cell carcinoma (OSCC). To study the function of AEBP1 in CAFs, we knocked down AEBP1 in CAFs isolated from surgically resected primary OSCCs. We found that genes associated with cell cycle were significantly affected by AEBP1 knockdown in CAFs.

2023-09-13 | GSE234220 | GEO

Effects of AEBP1 knockdown on gene expression profiles in human skeletal muscle myoblasts

Project description:We recently identified adipocyte enhancer binding protein 1 (AEBP1) as a novel cancer stroma-associated gene and reported that AEBP1 activates cancer-associated fibroblasts in oral cancer. In this study, we show that AEBP1 is negatively associated with skeletal muscle cell differentiation. We found that AEBP1 is downregulated during the diffraction of human skeletal muscle myoblasts (HSMMs). Microarray analysis revealed that knockdown of AEBP1 significantly upregulated a number of genes associated with myogenesis in HSMMs. Notably, co-culture of HSMMs with oral squamous cell carcinoma cells resulted in downregulation of muscle-related genes and upregulation of AEBP1 in HSMMs.

2024-11-14 | GSE268740 | GEO

Transcriptomic Analysis of Endothelial Cells from Fibrovascular Membranes in Proliferative Diabetic Retinopathy

Project description:Purpose: Identification of RUNX1 via next-generation sequencing (NGS) of fibrovascular membranes in patients with proliferative diabetic retinopathy. Methods: Transcriptomic analysis with Illumina HiSeq2000 of fibrovascular membrane and control retina CD31+ samples. The sequence reads were analyzed with ANOVA (ANOVA) and targets with significance (fold change > +/-1.5 and p-value < 0.05) were selected for with Cufflinks, DeSeq2, Partek E/M, and EdgeR. qRT–PCR validation was performed using SYBR Green assays along with Western blots, siRNA, and MUSE proliferation assays. Results: Using an optimized data analysis workflow, we mapped sequence reads per sample to the human genome (hg19) and identified genes that were statistically significant in all four statistical packages. P-values ranged from 8.78E-10 to 0.05. Using this gene list for ontology, highly significant annotation clusters included inflammatory, vascular development, and cell adhesion pathways. Conclusions: Our study represents the first detailed transcriptomic analysis of CD31+ cells from fibrovascular membrane and CD31+ cells from control retinas with biologic replicates, generated by RNA-seq technology. The preferential selection of inflammatory and angiogenic pathways using this gene list is highly consistent with DR pathogenesis, which involves leaky and aberrant vessel growth.

2017-04-04 | GSE94019 | GEO

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