Cancers (Mar 2021)
Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer
- 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
Affiliations
- Martina K. Zowada
- Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany
- Stephan M. Tirier
- Division of Theoretical Bioinformatics, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Sebastian M. Dieter
- Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany
- Teresa G. Krieger
- Division of Theoretical Bioinformatics, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Ava Oberlack
- Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany
- Robert Lorenz Chua
- Division of Theoretical Bioinformatics, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Mario Huerta
- Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany
- Foo Wei Ten
- Division of Theoretical Bioinformatics, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Karin Laaber
- Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany
- Jeongbin Park
- Division of Theoretical Bioinformatics, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Katharina Jechow
- Division of Theoretical Bioinformatics, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Torsten Müller
- Division of Proteomics of Stem Cells and Cancer, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Mathias Kalxdorf
- Division of Proteomics of Stem Cells and Cancer, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Mark Kriegsmann
- Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany
- Katharina Kriegsmann
- Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, 69120 Heidelberg, Germany
- Friederike Herbst
- Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany
- Jeroen Krijgsveld
- Division of Proteomics of Stem Cells and Cancer, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Martin Schneider
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany
- Roland Eils
- Division of Theoretical Bioinformatics, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Hanno Glimm
- Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany
- Christian Conrad
- Division of Theoretical Bioinformatics, DKFZ Heidelberg, 69120 Heidelberg, Germany
- Claudia R. Ball
- Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany
- DOI
- https://doi.org/10.3390/cancers13051097
- Journal volume & issue
-
Vol. 13,
no. 5
p. 1097
Abstract
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.
Keywords
- colorectal cancer
- tumor-initiating cells
- tumor heterogeneity
- patient-derived cancer models
- single-cell RNA-sequencing
- tumor metabolism