Multimodal single-cell analyses reveal mechanisms of perianal fistula in diverse patients with Crohn's disease.

ABSTRACT:

Background

Crohn's disease complicated by perianal fistulae is more prevalent and severe in patients of African ancestry.

Methods

We profiled single cells from diverse patients with Crohn's disease with perianal fistula from colorectal mucosa and fistulous tracts. Immunofluorescence was performed to validate predicted cell-cell interactions. Unstimulated monocytes were chronically cultured in diverse cohorts. A subset was analyzed by single-nucleus RNA + ATAC sequencing.

Findings

Fistulous tract cells from complete proctectomies demonstrated enrichment of myeloid cells compared to paired rectal tissues. Ligand-receptor analysis highlights myeloid-stromal cross-talk and cellular senescence, with cellular co-localization validated by immunofluorescence. Chitinase-3 like

SUBMITTER: Levantovsky RM 

PROVIDER: S-EPMC11317226 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature