Single-cell and spatial transcriptomics reveal aberrant lymphoid developmental programs driving granuloma formation.

ABSTRACT: Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organs. 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 repurposes 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 reprogramm

SUBMITTER: Krausgruber T 

PROVIDER: S-EPMC9942876 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature