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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Chen, K-Y; Srinivasan, T; Lin, C; Tung, K-L; Gao, Z; Hsu, DS; Lipkin, SM; Shen, X

Published Date

  • July 2018

Published In

  • Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Annual International Conference

Volume / Issue

  • 2018 /

Start / End Page

  • 2378 - 2381

PubMed ID

  • 30440885

Pubmed Central ID

  • PMC6317967

Electronic International Standard Serial Number (EISSN)

  • 2694-0604

International Standard Serial Number (ISSN)

  • 2375-7477

Digital Object Identifier (DOI)

  • 10.1109/embc.2018.8512784

Language

  • eng