Single Cell Transcriptome Signatures of Sarcoidosis in Lung Immune Cell Populations

转录组 结节病 免疫系统 细胞 生物 计算生物学 免疫学 医学 病理 基因 基因表达 内科学 遗传学
作者
Camille M. Moore,Shu‐Yi Liao,Cheyret Wood,Abhimanyu Sarkar,Jonathan Cardwell,Kristyn MacPhail,Margaret M. Mroz,Christina Riley,Kara J. Mould,Clara I. Restrepo,Li Li,Lisa Maier,Ivana V. Yang
标识
DOI:10.1101/2025.01.20.633917
摘要

To identify cell specific molecular changes associated with sarcoidosis risk and progression, we aimed to characterize the cellular composition, gene expression patterns, and cell-cell interactions in BAL cells from patients with sarcoidosis (both progressive and non-progressive) and healthy controls. Single cell RNA-seq data were collected on 12 sarcoidosis and 4 control participants. We combined scRNA-seq data from these participants with our previously collected data on 4 sarcoidosis and 10 control participants for a final sample size of 16 sarcoidosis cases (8 progressive and 8 non-progressive) and 14 controls. Following initial preprocessing in CellRanger, data were quality controlled, combined, and clustered in Seurat. We tested differences in cell proportions by disease group using F-tests on cell proportions and differences in gene expression using pseudobulk analysis. Cell to cell communication and pathway analysis were performed using CellChat. We identified five macrophage populations: resident, high metallothionein (MT) resident, recruited, profibrotic recruited, and proliferating macrophages. Each subpopulation displayed unique gene expression profiles, with notable differential expression of genes and pathways linked to sarcoidosis in resident macrophages, recruited macrophages, and proliferating macrophages. We also observed changes in gene expression associated with disease progression in resident and recruited macrophages. In non-macrophages cells, we observed a significant reduction in the number of B cells in sarcoidosis patients compared to controls. Among T cell populations, we identified specific transcriptional alterations at gene and pathway level. Additionally, we observed distinct differences in cell-to-cell interactions of macrophages and T cells between sarcoidosis patients and healthy controls. These findings underscore the complexity of immune cell involvement in sarcoidosis and highlight potential cellular and molecular targets for further investigation.
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