Generation of intestinal chemosensory cells from nonhuman primate organoids

Inaba, Akihiko; Kumaki, Shunsuke; Arinaga, Ayane; Tanaka, Keisuke; Aihara, Eitaro; Yamane, Takumi; Oishi, Yoshifumi; Imai, Hiroo; Iwatsuki, Ken

doi:10.1016/j.bbrc.2020.12.044

Cited by 6 publications

(9 citation statements)

References 28 publications

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“…IL-4 medium had a significant effect on DCLK1 expression ( Figure 1 d, Figure S1c,d ). As the efficiency of cell differentiation into tuft cells by IL-4 induction was maintained at the same level as in our previous report ( Figure S1c ) [ 12 ], the IF conditions were used for subsequent experiments.…”

Section: Resultsmentioning

confidence: 99%

“…We have recently reported on the generation of intestinal organoids from macaques [ 12 ] by modifying the original culture method of the human intestine, as described by Sato et al [ 21 ]. Recently, an improved method that replaced the p38 inhibitor (SB202190), as used in the original protocol, with IGF-1 and FGF-2 was reported by Fujii et al [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…As a result, we introduced an improved method to confirm cell proliferation and differentiation ( Supplementary Figure S1 ). With the improved culture conditions using IGF-1 and FGF-2, we tested whether Th2 cytokine stimulation promotes cell differentiation, as previously reported [ 12 ]. RNA-seq analysis and RT-PCR showed that IL-4 and IL-13 strongly induced tuft and goblet cell marker gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…The culture medium was prepared as follows. The basal medium and conventional proliferation medium, including SB202190 (FUJIFILM WAKO Pure Chemical Corporation, Osaka, Japan), were prepared as previously described [ 12 ]. Because an improved medium, with IGF-1 and FGF-2 instead of a p38 MAPK inhibitor (p38i) [ 22 ], was used for human organoid culture, we tested whether the improved media could be used in macaque organoids.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we reported on the generation of intestinal organoids from macaques to analyze the intestinal chemosensory cells of primates in vitro [ 12 ]. Since macaque organoids are able to differentiate into tuft cells by Th2 cytokines, this system provides a suitable model to explore the immune response of the intestinal epithelium in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate

Inaba

Arinaga

Tanaka

et al. 2021

IJMS

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In the intestine, the innate immune system excludes harmful substances and invading microorganisms. Tuft cells are taste-like chemosensory cells found in the intestinal epithelium involved in the activation of group 2 innate lymphoid cells (ILC2). Although tuft cells in other tissues secrete the neurotransmitter acetylcholine (ACh), their function in the gut remains poorly understood. In this study, we investigated changes in the expression of genes and cell differentiation of the intestinal epithelium by stimulation with interleukin-4 (IL-4) or IL-13 in macaque intestinal organoids. Transcriptome analysis showed that tuft cell marker genes were highly expressed in the IL-4- and IL-13-treated groups compared with the control, and the gene expression of choline acetyltransferase (ChAT), a synthesis enzyme of ACh, was upregulated in IL-4- and IL-13-treated groups. ACh accumulation was observed in IL-4-induced organoids using high-performance liquid chromatography-mass spectrometry (HPLC/MS), and ACh strongly released granules from Paneth cells. This study is the first to demonstrate ACh upregulation by IL-4 induction in primates, suggesting that IL-4 plays a role in Paneth cell granule secretion via paracrine stimulation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate

Inaba

Arinaga

Tanaka

et al. 2021

IJMS

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Intestinal organoids as an in vitro platform to characterize disposition, metabolism, and safety profile of small molecules

Kourula

Derksen²,

Jardi

et al. 2023

European Journal of Pharmaceutical Sciences

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Tuft Cells: Context- and Tissue-Specific Programming for a Conserved Cell Lineage

Kotas

O’Leary

Locksley

2023

Annu. Rev. Pathol. Mech. Dis.

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Tuft cells are found in tissues with distinct stem cell compartments, tissue architecture, and luminal exposures but converge on a shared transcriptional program, including expression of taste transduction signaling pathways. Here, we summarize seminal and recent findings on tuft cells, focusing on major categories of function—instigation of type 2 cytokine responses, orchestration of antimicrobial responses, and emerging roles in tissue repair—and describe tuft cell–derived molecules used to affect these functional programs. We review what is known about the development of tuft cells from epithelial progenitors under homeostatic conditions and during disease. Finally, we discuss evidence that immature, or nascent, tuft cells with potential for diverse functions are driven toward dominant effector programs by tissue- or perturbation-specific contextual cues, which may result in heterogeneous mature tuft cell phenotypes both within and between tissues. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 18 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Generation of intestinal chemosensory cells from nonhuman primate organoids

Cited by 6 publications

References 28 publications

Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate

Interleukin-4 Promotes Tuft Cell Differentiation and Acetylcholine Production in Intestinal Organoids of Non-Human Primate

Intestinal organoids as an in vitro platform to characterize disposition, metabolism, and safety profile of small molecules

Tuft Cells: Context- and Tissue-Specific Programming for a Conserved Cell Lineage

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