Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids.
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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https://hdl.handle.net/10161/17792Published Version (Please cite this version)
10.1109/embc.2018.8512784Publication Info
Chen, Kai-Yuan; Srinivasan, Tara; Lin, Christopher; Tung, Kuei-Ling; Gao, Ziyang;
Hsu, David S; ... Shen, Xiling (2018). Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal
Cancer Organoids. Conference proceedings : ... Annual International Conference of the IEEE Engineering
in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society.
Annual Conference, 2018. pp. 2378-2381. 10.1109/embc.2018.8512784. Retrieved from https://hdl.handle.net/10161/17792.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Xiling Shen
Adjunct Professor in the Department of Pathology
Dr. Shen’s research interests lie at precision medicine and systems biology. His lab
integrates engineering, computational and biological techniques to study cancer, stem
cells, microbiota and the nervous system in the gut. This multidisciplinary work has
been instrumental in initiating several translational clinical trials in precision
therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP)
and a core member of the Center for Genomics and Computational Biolog

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