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

Publication ,  Journal Article
Chen, K-Y; Srinivasan, T; Lin, C; Tung, K-L; Gao, Z; Hsu, DS; Lipkin, SM; Shen, X
Published in: Annu Int Conf IEEE Eng Med Biol Soc
July 2018

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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Published In

Annu Int Conf IEEE Eng Med Biol Soc

DOI

EISSN

2694-0604

Publication Date

July 2018

Volume

2018

Start / End Page

2378 / 2381

Location

United States

Related Subject Headings

  • Transcriptome
  • Single-Cell Analysis
  • Oxaliplatin
  • Organoids
  • Humans
  • Colorectal Neoplasms
  • Cell Culture Techniques
 

Citation

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Chicago
ICMJE
MLA
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Chen, K.-Y., Srinivasan, T., Lin, C., Tung, K.-L., Gao, Z., Hsu, D. S., … Shen, X. (2018). Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids. Annu Int Conf IEEE Eng Med Biol Soc, 2018, 2378–2381. https://doi.org/10.1109/EMBC.2018.8512784
Chen, Kai-Yuan, Tara Srinivasan, Christopher Lin, Kuei-Ling Tung, Ziyang Gao, David S. Hsu, Steven M. Lipkin, and Xiling Shen. “Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids.Annu Int Conf IEEE Eng Med Biol Soc 2018 (July 2018): 2378–81. https://doi.org/10.1109/EMBC.2018.8512784.
Chen K-Y, Srinivasan T, Lin C, Tung K-L, Gao Z, Hsu DS, et al. Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids. Annu Int Conf IEEE Eng Med Biol Soc. 2018 Jul;2018:2378–81.
Chen, Kai-Yuan, et al. “Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids.Annu Int Conf IEEE Eng Med Biol Soc, vol. 2018, July 2018, pp. 2378–81. Pubmed, doi:10.1109/EMBC.2018.8512784.
Chen K-Y, Srinivasan T, Lin C, Tung K-L, Gao Z, Hsu DS, Lipkin SM, Shen X. Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids. Annu Int Conf IEEE Eng Med Biol Soc. 2018 Jul;2018:2378–2381.

Published In

Annu Int Conf IEEE Eng Med Biol Soc

DOI

EISSN

2694-0604

Publication Date

July 2018

Volume

2018

Start / End Page

2378 / 2381

Location

United States

Related Subject Headings

  • Transcriptome
  • Single-Cell Analysis
  • Oxaliplatin
  • Organoids
  • Humans
  • Colorectal Neoplasms
  • Cell Culture Techniques