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Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis

ABSTRACT: Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis

PROVIDER: PRJNA791605 | ENA |

REPOSITORIES: ENA

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Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis [spatial transcriptomics data]

Project description:Purpose: Granulomas are lumps of immune cells that can form in various organs, causing chronic inflammation and tissue destruction. While most granulomas appear histologically heterogeneous and unstructured, they have a certain resemblance of lymphoid organ formation. We thus pursued the hypothesis that granuloma formation is a highly orchestrated process that mixes and repurposes various regulatory mechanisms of normal development Methods: We performed single-cell sequencing and spatial transcriptomics on granulomas from patients diagnosed with cutaneous sarcoidosis, and we bioinformatically reconstructed their gene-regulatory networks and cell-cell interactions Results: We observed regulatory processes underlying granuloma formation that were highly conserved across individuals and followed characteristic spatial patterns. We identified metabolically reprogrammed macrophages, various T cells subsets and structural cells including fibroblasts and endothelial cells as key players in granulomas. Specifically, exhausted interferon-gamma-producing Th17.1 cells with cytotoxic potential and inflammatory fibroblasts were identified as drivers of granuloma formation by attracting various immune cell types. Summary: we found that granuloma formation in sarcoidosis is a molecular and cellular process that adopts specific aspects of normal lymphoid organ development in aberrant combinations. Our study frames human granuloma formation as a developmental pathology and raises the future perspective of therapeutic targeting of granuloma-specific regulatory programs.

2023-02-07 | GSE192460 | GEO

Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis [single-cell sequencing]

2023-02-07 | GSE192456 | GEO

Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis [single-cell sequencing]

Project description:Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis [single-cell sequencing]

| PRJNA791608 | ENA

Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis [spatial transcriptomics data]

Project description:Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis [spatial transcriptomics data]

| PRJNA791612 | ENA

Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

Project description:Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis).

2020-12-09 | GSE157671 | GEO

Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

Project description:Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

| PRJNA662362 | ENA

Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-06 | GSE192461 | GEO

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis

Project description:Sarcoidosis is a granulomatous disease of unknown cause. We performed single-cell RNA sequencing to identify the macrophages that comprise sarcoidosis granulomas.

2023-09-25 | GSE234901 | GEO

Single-cell RNA-seq and spatial transcriptomics data for the sarcoidosis baseline project

Project description:Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organ formation. To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on granulomas from patients with sarcoidosis and bioinformatically reconstructed the underlying gene-regulatory networks. We discovered an immune stimulatory environment in granulomas that repurposed transcriptional programs associated with lymphoid organ development. Granuloma formation followed characteristic spatial patterns and involved genes linked to immunometabolism, cytokine and chemokine signaling, and extracellular matrix remodeling. Three cell types emerged as key players in granuloma formation: metabolically reprogrammed macrophages, cytokine-producing Th17.1 cells, and fibroblasts with inflammatory and tissue remodeling phenotypes. Pharmacological inhibition of one of the identified processes attenuated granuloma formation in a sarcoidosis mouse model. We show that human granulomas adopt characteristic aspects of normal lymphoid organ development in aberrant combinations, indicating that granulomas constitute aberrant lymphoid organs.

| EGAS00001006970 | EGA

Spatial profiling of human immune cells in sarcoidosis

Project description:Sarcoidosis is a multiorgan inflammatory disease that is characterized by tissue granulomas and remains so challenging for clinicians to diagnose that it has been called “the great imitator”. Here, by performing single-cell sequencing and spatial transcriptomics on skin granulomas from sarcoid and non-sarcoid patients, we discovered increased recruitment of innate lymphoid cells in granulomas. Sarcoid-associated cells exhibited increased cell migration compared to healthy individuals. Importantly, granuloma formation was attenuated in mice genetically lacking these cells or treated with a pharmacologic inhibitor.

2024-09-13 | GSE227041 | GEO

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