Cancer-associated fibroblasts (CAFs) reside within the tumor microenvironment, facilitating cancer progression and metastasis via direct and indirect interactions with cancer cells and other stromal cell types. CAFs are composed of heterogeneous subpopulations of activated fibroblasts, including myofibroblastic, inflammatory, and immunosuppressive CAFs. In this study, we sought to identify subpopulations of CAFs isolated from human lung adenocarcinomas and describe their transcriptomic and functional characteristics through single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatics analyses. Cell trajectory analysis of combined total and THY1 + CAFs revealed two branching points with five distinct branches. Based on Gene Ontology analysis, we denoted Branch 1 as “immunosuppressive”, Branch 2 as “neoantigen presenting”, Branch 4 as “myofibroblastic”, and Branch 5 as “proliferative” CAFs. We selected representative branch-specific markers and measured their expression levels in total and THY1 + CAFs. We also investigated the effects of these markers on CAF activity under coculture with lung cancer cells. This study describes novel subpopulations of CAFs in lung adenocarcinoma, highlighting their potential value as therapeutic targets.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (NRF-2018R1D1A1A02085738 to Y.H.K., NRF-2020R1A5A2019210 to Y.-H.A., NRF-2019R1C1C1010385 to K.K.) and the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1720100 to Y.H.K.).
© 2022 by the authors.
- cancer-associated fibroblasts
- lung adenocarcinoma
- single-cell RNA sequencing
- tumor microenvironment