Similar Datasets
Project description:Fibrosis, the replacement of healthy tissue with collagen-rich matrix, can occur following injury in almost every organ. Mouse lungs follow stereotyped sequences of fibrogenesis-to-resolution after bleomycin injury, and we reasoned that profiling post-injury histological progression could uncover pro- vs. anti-fibrotic features with functional value for human fibrosis. We mapped spatiotemporally-resolved transformations in lung extracellular matrix (ECM) architecture to spatially-resolved, multi-omic data. First, we charted stepwise trajectories of matrix aberration vs. resolution using unsupervised machine learning, denoting a reversible transition in uniform-to-disordered histological architecture. Single-cell sequencing along these trajectories identified temporally-enriched “ECM-secreting” (Csmd1+) and “pro-resolving” (Cd248+) fibroblasts, for which Visium inferred divergent histological signatures and spatial-transcriptional “neighborhoods”. Critically, pro-resolving fibroblast instillation helped ameliorate fibrosis in vivo. Further, fibroblast neighborhood-associated moieties, Serpine2 and Pi16, functionally modulated human lung fibrosis ex vivo. Spatial phenotyping of idiopathic pulmonary fibrosis further uncovered analogous fibroblast subtypes and neighborhoods in human disease. Collectively, these findings establish an atlas of pro-/anti-fibrotic factors underlying lung matrix architecture and implicate fibroblast-centered moieties in modulating fibrotic progression vs. resolution.
2025-01-07 | GSE250395 | GEO
Project description:Fibrosis, the replacement of healthy tissue with collagen-rich matrix, can occur following injury in almost every organ. Mouse lungs follow stereotyped sequences of fibrogenesis-to-resolution after bleomycin injury, and we reasoned that profiling post-injury histological progression could uncover pro- vs. anti-fibrotic features with functional value for human fibrosis. We mapped spatiotemporally-resolved transformations in lung extracellular matrix (ECM) architecture to spatially-resolved, multi-omic data. First, we charted stepwise trajectories of matrix aberration vs. resolution using unsupervised machine learning, denoting a reversible transition in uniform-to-disordered histological architecture. Single-cell sequencing along these trajectories identified temporally-enriched “ECM-secreting” (Csmd1+) and “pro-resolving” (Cd248+) fibroblasts, for which Visium inferred divergent histological signatures and spatial-transcriptional “neighborhoods”. Critically, pro-resolving fibroblast instillation helped ameliorate fibrosis in vivo. Further, fibroblast neighborhood-associated moieties, Serpine2 and Pi16, functionally modulated human lung fibrosis ex vivo. Spatial phenotyping of idiopathic pulmonary fibrosis further uncovered analogous fibroblast subtypes and neighborhoods in human disease. Collectively, these findings establish an atlas of pro-/anti-fibrotic factors underlying lung matrix architecture and implicate fibroblast-centered moieties in modulating fibrotic progression vs. resolution.
2025-01-07 | GSE250397 | GEO
Project description:Fibrosis, the replacement of healthy tissue with collagen-rich matrix, can occur following injury in almost every organ. Mouse lungs follow stereotyped sequences of fibrogenesis-to-resolution after bleomycin injury, and we reasoned that profiling post-injury histological progression could uncover pro- vs. anti-fibrotic features with functional value for human fibrosis. We mapped spatiotemporally-resolved transformations in lung extracellular matrix (ECM) architecture to spatially-resolved, multi-omic data. First, we charted stepwise trajectories of matrix aberration vs. resolution using unsupervised machine learning, denoting a reversible transition in uniform-to-disordered histological architecture. Single-cell sequencing along these trajectories identified temporally-enriched “ECM-secreting” (Csmd1+) and “pro-resolving” (Cd248+) fibroblasts, for which Visium inferred divergent histological signatures and spatial-transcriptional “neighborhoods”. Critically, pro-resolving fibroblast instillation helped ameliorate fibrosis in vivo. Further, fibroblast neighborhood-associated moieties, Serpine2 and Pi16, functionally modulated human lung fibrosis ex vivo. Spatial phenotyping of idiopathic pulmonary fibrosis further uncovered analogous fibroblast subtypes and neighborhoods in human disease. Collectively, these findings establish an atlas of pro-/anti-fibrotic factors underlying lung matrix architecture and implicate fibroblast-centered moieties in modulating fibrotic progression vs. resolution.
2025-01-07 | GSE250396 | GEO
Project description:Histological Signatures Reveal Anti-Fibrotic Factors in Mouse and Human Lungs
| PRJNA1053808 | ENA
Project description:Histological Signatures Reveal Anti-Fibrotic Factors in Mouse and Human Lungs [Visium]
| PRJNA1053812 | ENA
Project description:Histological Signatures Reveal Anti-Fibrotic Factors in Mouse and Human Lungs [scRNA-seq]
| PRJNA1053811 | ENA
Project description:Histological Signatures Reveal Anti-Fibrotic Factors in Mouse and Human Lungs [scATAC-Seq]
| PRJNA1053810 | ENA
Project description:Obesity is a major risk factor for a plethora of metabolic disturbances including diabetes and cardiovascular disease. Accumulating evidence is showing that there is an adipose tissue depot-dependent relationship with obesity-induced metabolic dysfunction. While some adipose depots, such as subcutaneous fat, are generally metabolically innocuous, others such as visceral fat, are directly deleterious. A lesser known visceral adipose depot is the pericardial adipose tissue depot. We therefore set out to examine its transcriptional and morphological signature under chow and high-fat fed conditions, in comparison with other adipose depots, using a mouse model. Our results revealed that under chow conditions pericardial adipose tissue has uncoupling-protein 1 gene expression levels which are significantly higher than classical subcutaneous and visceral adipose depots. We also observed that under high-fat diet conditions, the pericardial adipose depot exhibits greatly upregulated transcript levels of inflammatory cytokines. Our results collectively indicate, for the first time, that the pericardial adipose tissue possesses a unique transcriptional and histological signature which has features of both a beige (brown fat-like) but also pro-inflammatory depot, such as visceral fat. This unique profile may be involved in metabolic dysfunction associated with obesity.
| S-EPMC7353424 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-11-01 | GSE226376 | GEO
Project description:To further understand the pathologic microenvironment in IPF, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish normal and IPF lung in normal-looking, fibrotic foci and hyperplastic areas of IPF lung. Four IPF lungs were dissected into normal-looking, fibrotic foci and hyperplastic areas by Laser-Capture-Microdissection. Gene expression analysis showed that 638 significantly different genes were identified that clearly distinguished the different IPF microenvironments . Among them, MMP19 was revealed as one of the most significantly up-regulated genes that distinguished normal looking epithelial cells (N) to hyperplastic epithelial cells, MMP19 up-regulation in IPF lungs was verified by immunohistochemical (IHC), qRT-PCR and Western-blot. IPF lungs are heterogeneity complex, which comprise normal looking area, fibrotic foci and hyperplastic area. In this study we separated the normal, fibrotic foci and hyperplastic area by LCM and employed Agilent whole genome gene expression microarray profiling to identify genes with the potential to distinguish the unique microenironment of IPF
2013-01-11 | E-GEOD-35309 | biostudies-arrayexpress