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POU5F1 induces cellular heterogeneity in colorectal cancer

ABSTRACT: POU5F1 induces cellular heterogeneity in colorectal cancer

PROVIDER: PRJNA715744 | ENA |

REPOSITORIES: ENA

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POU5F1 induces cellular heterogeneity in colorectal cancer

Project description:In this study, we aimed to identify CRC treatment resistance mechanisms by focusing on POU5F1-positive cells. Despite the small number of POU5F1-positive cells, single POU5F1-expressing cells produced heterogeneous cell populations in vitro and in vivo colorectal cancer organod. This study unveils a mechanism of CRC treatment resistance and highlights the potential of POU5F1-expressing cells as CTCs.

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Project description:Intratumoralmheterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA–seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs). Additionally, epithelial–mesenchymal transition (EMT)-related genes were found to be upregulated only in the CAF subpopulation of tumor samples. Notably, colorectal tumors previously assigned to a single subtype on the basis of bulk transcriptomics could be divided into subgroups with divergent survival probability by using single-cell signatures, thus underscoring the prognostic value of our approach. Overall, our results demonstrate that unbiased single-cell RNA–seq profiling of tumor and matched normal samples provides a unique opportunity to characterize aberrant cell states within a tumor.

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