Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer

Intra-tumor heterogeneity of tumor-initiating cell (TIC) activity drives colorectal cancer (CRC) progression and therapy resistance. Here, we used single-cell RNA-sequencing of patient-derived CRC models to decipher distinct cell subpopulations based on their transcriptional profiles. Cell type-spec...

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Bibliographic Details
Published in:Cancers 2021-03, Vol.13 (5), p.1097
Main Authors: Zowada, Martina K, Tirier, Stephan M, Dieter, Sebastian M, Krieger, Teresa G, Oberlack, Ava, Chua, Robert Lorenz, Huerta, Mario, Ten, Foo Wei, Laaber, Karin, Park, Jeongbin, Jechow, Katharina, Müller, Torsten, Kalxdorf, Mathias, Kriegsmann, Mark, Kriegsmann, Katharina, Herbst, Friederike, Krijgsveld, Jeroen, Schneider, Martin, Eils, Roland, Glimm, Hanno, Conrad, Christian, Ball, Claudia R
Format: Article
Language:English
Subjects:
Cancer
Cell culture
Cell cycle
Cell differentiation
Colorectal cancer
Colorectal carcinoma
Epithelial cells
Gene expression
Hypoxia
Intestine
Medical prognosis
Metabolism
Mutation
Patients
Principal components analysis
Spheroids
Stem cells
Transcription
Tumors
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Summary:Intra-tumor heterogeneity of tumor-initiating cell (TIC) activity drives colorectal cancer (CRC) progression and therapy resistance. Here, we used single-cell RNA-sequencing of patient-derived CRC models to decipher distinct cell subpopulations based on their transcriptional profiles. Cell type-specific expression modules of stem-like, transit amplifying-like, and differentiated CRC cells resemble differentiation states of normal intestinal epithelial cells. Strikingly, identified subpopulations differ in proliferative activity and metabolic state. In summary, we here show at single-cell resolution that transcriptional heterogeneity identifies functional states during TIC differentiation. Furthermore, identified expression signatures are linked to patient prognosis. Targeting transcriptional states associated to cancer cell differentiation might unravel novel vulnerabilities in human CRC.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13051097