Functional states in tumor‐initiating cell differentiation in human colorectal cancer

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Martina K. Zowada - , German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT) Dresden, Heidelberg University  (Author)
  • Stephan M. Tirier - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Sebastian M. Dieter - , German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT) Dresden (Author)
  • Teresa G. Krieger - , German Cancer Research Center (DKFZ), Heidelberg University , Charité – Universitätsmedizin Berlin (Author)
  • Ava Oberlack - , German Cancer Research Center (DKFZ) (Author)
  • Robert Lorenz Chua - , German Cancer Research Center (DKFZ), Heidelberg University , Charité – Universitätsmedizin Berlin (Author)
  • Mario Huerta - , German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT) Dresden (Author)
  • Foo Wei Ten - , German Cancer Research Center (DKFZ), Heidelberg University , Charité – Universitätsmedizin Berlin (Author)
  • Karin Laaber - , German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT) Dresden, Heidelberg University  (Author)
  • Jeongbin Park - , German Cancer Research Center (DKFZ), Charité – Universitätsmedizin Berlin (Author)
  • Katharina Jechow - , German Cancer Research Center (DKFZ), Heidelberg University , Charité – Universitätsmedizin Berlin (Author)
  • Torsten Müller - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Mathias Kalxdorf - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Mark Kriegsmann - , Heidelberg University  (Author)
  • Katharina Kriegsmann - , Heidelberg University  (Author)
  • Friederike Herbst - , German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT) Dresden (Author)
  • Jeroen Krijgsveld - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Martin Schneider - , Heidelberg University  (Author)
  • Roland Eils - , German Cancer Research Center (DKFZ), Heidelberg University , Charité – Universitätsmedizin Berlin (Author)
  • Hanno Glimm - , National Center for Tumor Diseases Dresden, German Cancer Consortium (Partner: DKTK, DKFZ), German Cancer Research Center, partner site Dresden, German Cancer Research Center (DKFZ), University Hospital Carl Gustav Carus Dresden, National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Christian Conrad - , German Cancer Research Center (DKFZ), Heidelberg University , Charité – Universitätsmedizin Berlin (Author)
  • Claudia R. Ball - , National Center for Tumor Diseases Dresden, German Cancer Consortium (Partner: DKTK, DKFZ), German Cancer Research Center, partner site Dresden, German Cancer Research Center (DKFZ), University Hospital Carl Gustav Carus Dresden, National Center for Tumor Diseases (NCT) Heidelberg (Author)

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 sub-populations differ in proliferative activity and metabolic state. In summary, we here show at single-cell resolution that transcriptional heterogeneity identifies functional states during TIC differentia-tion. Furthermore, identified expression signatures are linked to patient prognosis. Targeting transcriptional states associated to cancer cell differentiation might unravel novel vulnerabilities in human CRC.

Details

Original languageEnglish
Article number1097
Pages (from-to)1-31
Number of pages31
JournalCancers
Volume13
Issue number5
Publication statusPublished - 1 Mar 2021
Peer-reviewedYes

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Colorectal cancer, Patient‐derived cancer models, Single‐cell RNA‐sequencing, Transcriptional programs, Tumor cell differentiation, Tumor heterogeneity, Tumor metabolism, Tumor‐initiating cells