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

Overview

Journal Annu Int Conf IEEE Eng Med Biol Soc

Specialty Biomedical Engineering

Date 2018 Nov 17

PMID 30440885

Citations 19

Authors

Kai-Yuan Chen

Tara Srinivasan

Christopher Lin

Kuei-Ling Tung

Ziyang Gao

David S Hsu

Steven M Lipkin

Xiling Shen

Affiliations

Soon will be listed here.

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.

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