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
Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.
Department of Translational Medical Oncology, NCT Dresden and DKFZ, 01307 Dresden, Germany.
Cancers (Basel). 2021 Mar 4;13(5):1097. doi: 10.3390/cancers13051097.
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.
肿瘤起始细胞（TIC）活性的肿瘤内异质性驱动结直肠癌（CRC）进展和治疗耐药性。在此，我们对患者来源的CRC模型进行单细胞RNA测序，以根据转录谱解析不同的细胞亚群。干细胞样、过渡扩增样和分化的CRC细胞的细胞类型特异性表达模块类似于正常肠上皮细胞的分化状态。引人注目的是，所鉴定的亚群在增殖活性和代谢状态方面存在差异。总之，我们在此以单细胞分辨率表明，转录异质性可识别TIC分化过程中的功能状态。此外，所鉴定的表达特征与患者预后相关。靶向与癌细胞分化相关的转录状态可能会揭示人类CRC中的新弱点。
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