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A4480 - Single Cell Analysis of Disease-Associated Macrophages in Lung Fibrosis
Author Block: A. Looney1, D. Aran2, L. Liu3, A. Hsu1, V. Fong1, D. Sheppard1, A. Abate3, A. Butte2, M. Bhattacharya1; 1Medicine, UCSF, San Francisco, CA, United States, 2Institute for Computational Health Sciences, UCSF, San Francisco, CA, United States, 3Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, CA, United States.
Introduction: Macrophages regulate inflammatory and fibrotic responses to injury in multiple organs, but appreciation of their functional heterogeneity has been limited by conventional marker-based flow sorting followed by bulk mRNA sequencing. Methods: Here we applied single cell mRNA sequencing to explore macrophage heterogeneity in bleomycin mouse model. Given the relatedness of myeloid subsets such as dendritic cells and macrophages, we developed a tool for unbiased annotation of single cells by comparison of each transcriptome to multiple published microarray and RNAseq datasets. Results: Focusing on the macrophage group, we detected multiple clusters with distinct gene expression profiles two weeks after injury. Two macrophage clusters unique to bleomycin injury were notable for high MHC class II expression. MHCII-high alveolar macrophages had increased capacity for degrading and taking up extracellular collagen and secreted factors that regulate fibroblast migration. Preliminary in vivo studies indicate that those macrophages originate from circulatory progenitors and can be adoptively transferred and retained in lung, which opens possibilities of cell-based therapies. Conclusions: In conclusion, our results demonstrate novel macrophage subsets that regulate the fibrotic response after injury. Our future studies will focus on elucidating in vivo function of different subset of macrophages in a context of lung fibrosis.