转录组
生物
纤维化
博莱霉素
巨噬细胞
细胞
免疫荧光
成纤维细胞
电池类型
肺
肺纤维化
体内
基因表达
癌症研究
细胞生物学
病理
基因
体外
免疫学
医学
遗传学
化疗
抗体
内科学
作者
Dvir Aran,Agnieszka P. Looney,Lulu Liu,Fong,A Hsu,Paul J. Wolters,Alessandro Abate,Atul J. Butte,Mihir K. Bhattacharya
摘要
Abstract Myeloid cells localize to peripheral tissues in a wide range of pathologic contexts. However, appreciation of distinct myeloid subtypes has been limited by the signal averaging inherent to bulk sequencing approaches. Here we applied single-cell RNA sequencing (scRNA-seq) to map cellular heterogeneity in lung fibrosis induced by bleomycin injury in mice. We first developed a computational framework that enables unbiased, granular cell-type annotation of scRNA-seq. This approach identified a macrophage subpopulation that was specific to injured lung and notable for high expression of Cx3cr1 + and MHCII genes. We found that these macrophages, which bear a gene expression profile consistent with monocytic origin, progressively acquire alveolar macrophage identity and localize to sites of fibroblast accumulation. Probing their functional role, in vitro studies showed a trophic effect of these cells on fibroblast activation, and ablation of Cx3cr1 -expressing cells suppressed fibrosis in vivo. We also found by gene set analysis and immunofluorescence that markers of these macrophages were upregulated in samples from patients with lung fibrosis compared with healthy controls. Taken together, our results uncover a specific pathologic subgroup of macrophages with markers that could enable their therapeutic targeting for fibrosis.
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