Open AccessSingle-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts
Author(s) -
Kaiyi Zhu,
Lingyi Cai,
Chenqian Cui,
Juan R. de los Toyos,
Dimitris Anastassiou
Publication year - 2021
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1009228
Subject(s) - stromal cell , adipose tissue , gene signature , biology , cancer associated fibroblasts , cancer cell , metastasis , cancer , cancer research , epithelial–mesenchymal transition , cell type , gene expression , stromal vascular fraction , pancreatic cancer , gene , cell , genetics , endocrinology
During the last ten years, many research results have been referring to a particular type of cancer-associated fibroblasts associated with poor prognosis, invasiveness, metastasis and resistance to therapy in multiple cancer types, characterized by a gene expression signature with prominent presence of genes COL11A1 , THBS2 and INHBA . Identifying the underlying biological mechanisms responsible for their creation may facilitate the discovery of targets for potential pan-cancer therapeutics. Using a novel computational approach for single-cell gene expression data analysis identifying the dominant cell populations in a sequence of samples from patients at various stages, we conclude that these fibroblasts are produced by a pan-cancer cellular transition originating from a particular type of adipose-derived stromal cells naturally present in the stromal vascular fraction of normal adipose tissue, having a characteristic gene expression signature. Focusing on a rich pancreatic cancer dataset, we provide a detailed description of the continuous modification of the gene expression profiles of cells as they transition from APOD -expressing adipose-derived stromal cells to COL11A1 -expressing cancer-associated fibroblasts, identifying the key genes that participate in this transition. These results also provide an explanation to the well-known fact that the adipose microenvironment contributes to cancer progression.