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

• Main Authors: Martina K. Zowada, Stephan M. Tirier, Sebastian M. Dieter, Teresa G. Krieger, Ava Oberlack, Robert Lorenz Chua, Mario Huerta, Foo Wei Ten, Karin Laaber, Jeongbin Park, Katharina Jechow, Torsten Müller, Mathias Kalxdorf, Mark Kriegsmann, Katharina Kriegsmann, Friederike Herbst, Jeroen Krijgsveld, Martin Schneider, Roland Eils, Hanno Glimm, Christian Conrad, Claudia R. Ball
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Cancers
• Subjects: colorectal cancer; tumor-initiating cells; tumor heterogeneity; patient-derived cancer models; single-cell RNA-sequencing; tumor metabolism
• Online Access: https://www.mdpi.com/2072-6694/13/5/1097

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.