NHLBI TOPMed – NHGRI: INSIGHTS Study: Insights into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers Study
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PROVIDER: PRJNA1279277 | ENA |
REPOSITORIES: ENA
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Project description:NHLBI TOPMed – NHGRI: INSIGHTS Study: Insights into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers Study
| PRJNA1279276 | ENA
Project description:to gain a better understanding on the genomic mechanisms involved in defective healing in diabetes, we characterized here the gene expression profile and gene-gene interaction network of cultured fibroblasts derived from chronic diabetic leg ulcers comparatively to fibroblast obtained from control donors. Comparative transcriptomic analysis of cultured fibroblasts derived from six diabetic leg ulcers and five control fibroblasts using DNA microarrays and bioinformatics tools for studying gene-gene interaction networks.
2013-10-30 | E-GEOD-26365 | biostudies-arrayexpress
Project description:Venous leg ulcers (VLUs) are the most common cause of leg ulcers, yet only 44% heal with standard of care, highlighting the critical need for better understanding of their cellular pathology. We used a combination of single-cell RNA-Sequencing (scRNA-Seq) and bulk RNA-Seq to identify molecular mechanisms and cellular functions contributing to VLU pathophysiology. scRNA-Seq of chronic VLUs revealed impairments in immune, lymph-endothelial, and endothelial cells, along with the underlying signaling pathways. Next, RNA-Seq was performed to asses clinical outcomes in patients receiving standard of care, with wound healing rate monitored for at least 4 weeks. Transcriptomes of healing and non-healing VLUs were compared to those of human acute wounds (AW), revealing a robust suppression of inflammatory response, lymphangiogenesis and angiogenesis in non-healing VLUs. In contrast, healing VLUs resembled gene expression signature of physiological, acute wound healing. Reduced inflammatory response resulting from impaired leukocyte transmigration and egression, with suppression of kinases’ activity, including AKT, ERK, JNK1/2, SRC, and PDGFR, underlines the non-healing VLU signature. Bioinformatic analyses pinpointed PTEN as a master regulator of these processes and signaling pathways. Indeed, increased PTEN was confirmed in non-healing compared to healing VLUs, both on scRNA-Seq and protein levels. Functional in vivo murine studies confirmed that pharmacological PTEN inhibition enhanced immune response and proinflammatory signals, angiogenesis and lymphangiogenesis which resulted in accelerated wound closure. We identified PTEN as a master regulator of non-healing phenotype controlling multiple key processes responsible for impaired healing, underscoring its potential use as diagnostic and therapeutic target to promote wound closure in VLUs.
2026-06-09 | GSE314138 | GEO
Project description:Transcriptome analysis was performed to systematically compare human tuberculous ulcers with non-tuberculous skin ulcers. Focusing on the former, this study aimed to identify key associated genes, elucidate their expression profiles and functional attributes, and preliminarily dissect the molecular mechanisms governing their pathological progression. By bridging the current gap in the genetic characterization of tuberculous ulcers, this research not only provides novel targets for investigating disease pathogenesis but also establishes an experimental foundation for early clinical diagnosis and targeted therapeutic strategies, thereby holding significant implications for advancing disease prevention and management.（This study used Agilent Human lncRNA V6 microarray. Only normalized expression data were submitted, original raw scan files are not available.）
2026-06-11 | GSE331511 | GEO
Project description:Chronic non-healing venous leg ulcers (VLUs) are a widespread debilitating disease with high morbidity and associated costs, as approximately $15 billion annually are spent on the care of VLUs. Despite their socioeconomic burden, there is a paucity of novel treatments targeted towards healing VLUs, which can be attributed to both lack of pathophysiologic insight into VLU development as well as lack of knowledge regarding biologic actions of VLU-targeted therapies. Currently, the bioengineered bilayered living cellular construct (BLCC) skin substitute is the only FDA-approved biologic treatment for healing VLUs. To elucidate the mechanisms through which the BLCC promotes healing of chronic VLUs, we conducted a clinical trial (NCT01327937) in which patients with non-healing VLUs were treated with either standard care (compression therapy) or with BLCC together with standard care. Tissue was collected from the VLU edge before and 1 week after treatment, and samples underwent comprehensive microarray, mRNA and protein analyses. Ulcers treated with BLCC skin substitute displayed three distinct patterns suggesting the mechanisms by which BLCC shifted a non-healing into a healing tissue response: it modulated inflammatory and growth factor signaling; it activated keratinocytes; and it attenuated Wnt/β-catenin signaling. In these ways, BLCC application orchestrated a shift of the chronic non-healing ulcer microenvironment into a distinctive healing milieu resembling that of an acute, healing wound. Our findings also provide first patient-derived in vivo evidence of specific biologic processes that can be targeted in the design of therapies to promote healing of chronic VLUs.
2016-09-01 | GSE84571 | GEO
Project description:RNA-Seq was performed on healing and non-healing venous leg ulcers, and transcriptomes were compared to those of human acute wounds (AW). A robust suppression of inflammatory response, lymphangiogenesis and angiogenesis was hallmark of non-healing, in contrast to healing VLUs that showed similarity to physiological healing. Diminished inflammatory response in non-healing VLUs was due to impaired leukocyte transmigration and egression, with suppression of kinases’ activity, including AKT, ERK, JNK1/2, SRC, and PDGFR, underlining the non-healing signature. Bioinformatic analyses pinpointed PTEN as a master negative regulator of the processes and signaling pathways suppressed in non-healing VLU. Indeed, increased PTEN was confirmed in non-healing compared to healing VLUs on scRNA-Seq and protein level. Functional in vivo murine studies confirmed that pharmacological PTEN inhibition enhances immune response, and proinflammatory signals, leading to accelerated wound closure. We identify PTEN as a master regulator of non-healing VLU phenotype that orchestrates multiple key processes responsible for impaired healing. Targeting PTEN as a therapeutic approach may shift non-healing VLUs into healing trajectory allowing for progression of wound closure.
2025-11-14 | GSE279534 | GEO
Project description:Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. Keywords: ChIP/chip NHGRI Menin ChIP-Chip
2006-07-24 | E-GEOD-5357 | biostudies-arrayexpress
Project description:PTEN, a master driver of nonhealing phenotype in venous leg ulcers, suppresses immune response, angiogenesis and lymphangiogenesis
| PRJNA1173211 | ENA
Project description:Screening and functional study of genes related to tuberculous ulcers
| PRJNA1468531 | ENA