具体来龙去脉大家可以自行阅读发表于2020的文章,标题 是:《Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma》,数据集在;https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138709
首先看正文描述:2,941 high-quality fibro- blasts that were clustered into 6 subpopulations, of which 5 fibroblast clusters (subcluster 0, 1, 2, 3, 4) were mainly enriched in ICC tissues, whereas subcluster 5 was mainly present in adjacent tissues
Subcluster 0 fibroblasts accounted for the majority of the fibroblast populations (57.6%) and were characterized by microvasculature signature genes such as CD146 (MCAM), MYH11, GJA4, and RGS5, as well as inflammatory chemokines such as IL-6 and CCL8 (Fig. 4E). Thus, we designated them as vascular CAFs (vCAFs, vCAFs-c0-MCAM). Gene ontology (GO) analysis of vCAFs indicated significant enrichment for muscle contraction, response to hypoxia, and mesenchymal cell prolif- eration, consistent with their microvascular signatures (Fig. 4F).
Subcluster 1 fibroblasts expressed low levels of a-SMA but high levels of extracellular matrix (ECM) signatures, including collagen molecules (COL5A1, COL5A2, and COL6A3), periostin (POSTN), FN1, LUM, DCN, and VCAN. Interestingly, the GO terms enriched for this subtype were associated with ECM and collagen fibril organization, so we accordingly designated them as matrix CAFs (mCAFs, mCAFs–c1–POSTN, Fig. 4E, F). Like mCAFs–c1–POSTN,
Subcluster 2 fibroblasts expressed low levels of a-SMA but high levels of FBLN1, IGFI, CXCL1, IGFBP6, SLPI, SAA1, and complement genes (C3 and C7). In addition, the GO terms enriched for this Subcluster were related to ECM, inflammatory response regulation, and complement activation, indicating that this Subcluster may engage in immune modulation. Accordingly, fibroblasts in this Subcluster were named inflammatory CAFs (iCAFs, iCAFs–c2–FBLN1; Fig. 4E, F). Consistent with a previous report of mouse KPC tumors (Kras+/LSL-G12D; Trp53+/LSL- R172H; Pdx1-Cre) and human pancreatic ductal adenocarcinoma (PDAC),25 we found that
Subcluster 3 fibroblasts expressed major histocompatibility complex II (MHC-II) genes such as CD74, HLA- DRA, and HLA-DRB1. Moreover, the GO terms enriched in this Subcluster were related to leukocyte cell-cell adhesion, response to IFN-c, antigen processing, and antigen presentation via MHC- II; we therefore termed them antigen-presenting CAFs (apCAFs, apCAFs–c3–CD74; Fig. 4E, F).
Subcluster 4 fibroblasts mainly expressed epithelium-specific marker genes such as KRT19, KRT8, and SAA1, which we designated as EMT-like CAFs (eCAFs, eCAFs–c4–KRT19; Fig. 4D). Finally,
Subcluster 5 fibroblasts were mainly derived from adjacent tissues and expressed high levels of lipid metabolism and processing related genes, including APOA2, FABP1, FABP4, and FRZB, therefore, we named them lip- ofibroblast–c5–FABP1 (Fig. 4D).
很完美的生物学解释,:
Subcluster 0 被作者定义为 vascular CAFs ,高表达 GJA4, and RGS5 等
Subcluster 1 被作者定义为 matrix CAFs ,高表达 LUM, DCN, and VCAN等