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  2. Droplet-engineered organoids recapitulate parental tissue transcriptome with inter-organoid homogeneity and inter-tumor cell heterogeneity

Droplet-engineered organoids recapitulate parental tissue transcriptome with inter-organoid homogeneity and inter-tumor cell heterogeneity

  • Fundam Res. 2022 Jun 3;4(6):1506-1514. doi: 10.1016/j.fmre.2022.05.018.
Haoran Zhao 1 2 Yifan Cheng 1 2 Jiawei Li 1 2 Jiaqi Zhou 1 2 Haowei Yang 1 2 Feng Yu 1 2 Feihong Yu 1 Davit Khutsishvili 1 2 Zitian Wang 1 2 Shengwei Jiang 1 2 Kaixin Tan 3 Yi Kuang 3 4 Xinhui Xing 1 Shaohua Ma 1 2
Affiliations

Affiliations

  • 1 Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen 518055, China.
  • 2 Tsinghua-Berkeley Shenzhen Institute (TBSI), Shenzhen 518055, China.
  • 3 Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong 999077, China.
  • 4 HKUST Shenzhen Research Institute, Shenzhen 518057, China.
Abstract

Organoids are expected to function as effective human organ models for precision Cancer studies and drug development. Currently, primary tissue-derived organoids, termed non-engineered organoids (NEOs), are produced by manual pipetting or liquid handling that compromises organoid-organoid homogeneity and organoid-tissue consistency. Droplet-based microfluidics enables automated Organoid production with high organoid-organoid homogeneity, organoid-tissue consistency, and a significantly improved production spectrum. It takes advantage of droplet-encapsulation of defined populations of cells and droplet-rendered microstructures that guide cell self-organization. Herein, we studied the droplet-engineered organoids (DEOs), derived from mouse liver tissues and human liver tumors, by using transcriptional analysis and cellular deconvolution on bulk RNA-seq data. The characteristics of DEOs are compared with the parental liver tissues (or tumors) and NEOs. The DEOs are proven higher reproducibility and consistency with the parental tissues, have a high production spectrum and shortened modeling time, and possess inter-organoid homogeneity and inter-tumor cell heterogeneity.

Keywords

Droplet-based microfluidics; Droplet-engineered organoid; Liver organoid; RNA-seq; Tumor.

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