Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts
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...
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| Veröffentlicht in: | PLoS computational biology 2021-07, Vol.17 (7), p.e1009228-e1009228 |
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| creator | Zhu, Kaiyi Cai, Lingyi Cui, Chenqian de los Toyos, Juan R Anastassiou, Dimitris |
| description | 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. |
| doi_str_mv | 10.1371/journal.pcbi.1009228 |
| format | Article |
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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.</description><identifier>ISSN: 1553-7358</identifier><identifier>ISSN: 1553-734X</identifier><identifier>EISSN: 1553-7358</identifier><identifier>DOI: 10.1371/journal.pcbi.1009228</identifier><identifier>PMID: 34283835</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Adipose tissue ; Adipose tissues ; Algorithms ; Biology and Life Sciences ; Breast cancer ; Cancer ; Cancer invasiveness ; Colorectal cancer ; Computer applications ; Data analysis ; Datasets ; Fibroblasts ; Gene expression ; Genes ; Health aspects ; Invasiveness ; Medical prognosis ; Medicine and Health Sciences ; Metastases ; Metastasis ; Microenvironments ; Oncology, Experimental ; Ovarian cancer ; Pancreatic cancer ; Physiological aspects ; Quorum sensing ; Stem cells ; Stromal cells</subject><ispartof>PLoS computational biology, 2021-07, Vol.17 (7), p.e1009228-e1009228</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Zhu et al. 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Kaiyi</au><au>Cai, Lingyi</au><au>Cui, Chenqian</au><au>de los Toyos, Juan R</au><au>Anastassiou, Dimitris</au><au>Rzhetsky, Andrey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts</atitle><jtitle>PLoS computational biology</jtitle><date>2021-07-20</date><risdate>2021</risdate><volume>17</volume><issue>7</issue><spage>e1009228</spage><epage>e1009228</epage><pages>e1009228-e1009228</pages><issn>1553-7358</issn><issn>1553-734X</issn><eissn>1553-7358</eissn><abstract>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. 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| subjects | Adipose tissue Adipose tissues Algorithms Biology and Life Sciences Breast cancer Cancer Cancer invasiveness Colorectal cancer Computer applications Data analysis Datasets Fibroblasts Gene expression Genes Health aspects Invasiveness Medical prognosis Medicine and Health Sciences Metastases Metastasis Microenvironments Oncology, Experimental Ovarian cancer Pancreatic cancer Physiological aspects Quorum sensing Stem cells Stromal cells |
| title | Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts |
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