Heterogeneous metabolic signatures are linked to cancer cell differentiation in colorectal cancer

Colorectal cancer (CRC) is characterized by functional intratumor heterogeneity that shares many similarites with the hierarchical organization of the normal intestinal epithelium. In order to relate transcriptional subtypes to functional tumor cell heterogeneity we applied scRNA-seq to 12 patient-derived CRC spheroid cultures. We identified shared expression programs that relate to intestinal lineages and revealed metabolic signatures that are linked to cancer cell differentiation. In addition, we validated and complemented sequencing results by quantitative microscopy using live-dyes and multiplexed RNA fluorescence in situ hybridization, thereby revealing metabolic compartmentalization and potential cell-cell interactions. FInally, we demonstrate functional differences between metabolically distinct lineage subtypes that might have strong implications for future treatment strategies of CRC.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 2 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001005524	Colorectal cancer (CRC) is characterized by functional intratumor heterogeneity that shares many similarites with the hierarchical organization of the normal intestinal epithelium. In order to relate transcriptional subtypes to functional tumor cell heterogeneity we applied scRNA-seq to 12 patient-derived CRC spheroid cultures. We identified shared expression programs that relate to intestinal lineages and revealed metabolic signatures that are linked to cancer cell differentiation. In addition, we validated and complemented sequencing results by quantitative microscopy using live-dyes and multiplexed RNA fluorescence in situ hybridization, thereby revealing metabolic compartmentalization and potential cell-cell interactions. Finally, we demonstrate functional differences between metabolically distinct lineage subtypes that might have strong implications for future treatment strategies of CRC.	NextSeq 500	8714

Publications	Citations
Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer. Zowada MK, Tirier SM, Dieter SM, Krieger TG, Oberlack A, Chua RL, Huerta M, Ten FW, Laaber K, Park J, Jechow K, Müller T, Kalxdorf M, Kriegsmann M, Kriegsmann K, Herbst F, Krijgsveld J, Schneider M, Eils R, Glimm H, Conrad C, Ball CR. Cancers (Basel) 13: 2021 1097	7
Intestinal cellular heterogeneity and disease development revealed by single-cell technology. Wang Y, Song W, Yu S, Liu Y, Chen YG. Cell Regen 11: 2022 26	5