Generation of intestinal chemosensory cells from nonhuman primate organoids

• Published in: Biochemical and biophysical research communications 2021-01, Vol.536, p.20-25
• Main Authors: Inaba, Akihiko, Kumaki, Shunsuke, Arinaga, Ayane, Tanaka, Keisuke, Aihara, Eitaro, Yamane, Takumi, Oishi, Yuichi, Imai, Hiroo, Iwatsuki, Ken
• Format: Article
• Language: English
• Subjects: Animals; Cell Culture Techniques - methods; Cell Differentiation - drug effects; Cell Lineage - drug effects; Chemosensory; Dibenzazepines - pharmacology; Enteroendocrine Cells - cytology; Interleukin-4 - pharmacology; Intestine; Intestines - cytology; Macaca; Organoid; Organoids - cytology; Primate
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.12.044

Several gastrointestinal epithelial cells are involved in taste signal transduction. Although rodent tissues are extensively used as a human gut model, recent studies show that the chemical sensing system in rodents differs from that in humans. Nonhuman primates in biomedical research are valuable animal models to advance our understanding of biological responses in humans. The 3D organoid culture produces functional gastrointestinal epithelial cells in vitro and can be generated from animal and human tissues. Here, we report the generation of intestinal chemosensory cells from nonhuman primates, macaques, using an organoid culture system. We were able to maintain macaque intestinal organoids in the proliferation medium for more than six months. Upon switching to differentiation medium, we observed a drastic change in organoid morphology and chemosensory cell marker protein expression. This switch from proliferation to differentiation was confirmed by transcriptome analysis of the duodenum, jejunum, and ileum organoids. We further observed that the supplementation of culture media with interleukin (IL)-4 or the Notch inhibitor dibenzazepine (DBZ) accelerated terminal cell differentiation into chemosensory cells. Overall, we generated monkey intestinal organoids for the first time. These organoids are suitable for studying the function of primate chemosensory cells. [Display omitted] •Intestinal organoids were generated from macaques for the first time.•These intestinal organoids could be maintained for more than six months.•Intestinal organoids differentiation could be promoted by IL-4 and DBZ.•Macaque intestinal organoids are suitable model to study primate chemosensory cells.