Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids.

TitleSingle-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids.
Publication TypeJournal Article
Year of Publication2018
AuthorsChen, K-Y, T Srinivasan, C Lin, K-L Tung, Z Gao, DS Hsu, SM Lipkin, and X Shen
JournalConference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Annual Conference
Volume2018
Start Page2378
Pagination2378 - 2381
Date Published07/2018
Abstract

Organoids are three-dimensional cell cultures that mimic organ functions and structures. The organoid model has been developed as a versatile in vitro platform for stem cell biology and diseases modeling. Tumor organoids are shown to share ~ 90% of genetic mutations with biopsies from same patients. However, it's not clear whether tumor organoids recapitulate the cellular heterogeneity observed in patient tumors. Here, we used single-cell RNA-Seq to investigate the transcriptomics of tumor organoids derived from human colorectal tumors, and applied machine learning methods to unbiasedly cluster subtypes in tumor organoids. Computational analysis reveals cancer heterogeneity sustained in tumor organoids, and the subtypes in organoids displayed high diversity. Furthermore, we treated the tumor organoids with a first-line cancer drug, Oxaliplatin, and investigated drug response in single-cell scale. Diversity of tumor cell populations in organoids were significantly perturbed by drug treatment. Single-cell analysis detected the depletion of chemosensitive subgroups and emergence of new drug tolerant subgroups after drug treatment. Our study suggests that the organoid model is capable of recapitulating clinical heterogeneity and its evolution in response to chemotherapy.

DOI10.1109/EMBC.2018.8512784
Short TitleConference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Annual Conference