Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

Gui Wei He; Lin Lin; Jeff DeMartino; Xuan Zheng; Nadzeya Staliarova; Talya Dayton; Harry Begthel; Willine J. van de Wetering; Eduard Bodewes; Jeroen van Zon; Sander Tans; Carmen Lopez-Iglesias; Peter J. Peters; Wei Wu; Daniel Kotlarz; Christoph Klein; Thanasis Margaritis; Frank Holstege; Hans Clevers

doi:10.1016/j.stem.2022.08.002

Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

Gui Wei He, Lin Lin, Jeff DeMartino, Xuan Zheng, Nadzeya Staliarova, Talya Dayton, Harry Begthel, Willine J. van de Wetering, Eduard Bodewes, Jeroen van Zon, Sander Tans, Carmen Lopez-Iglesias, Peter J. Peters, Wei Wu, Daniel Kotlarz, Christoph Klein, Thanasis Margaritis, Frank Holstege, Hans Clevers

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

Opposing roles have been proposed for IL-22 in intestinal pathophysiology. We have optimized human small intestinal organoid (hSIO) culturing, constitutively generating all differentiated cell types while maintaining an active stem cell compartment. IL-22 does not promote the expansion of stem cells but rather slows the growth of hSIOs. In hSIOs, IL-22 is required for formation of Paneth cells, the prime producers of intestinal antimicrobial peptides (AMPs). Introduction of inflammatory bowel disease (IBD)-associated loss-of-function mutations in the IL-22 co-receptor gene IL10RB resulted in abolishment of Paneth cells in hSIOs. Moreover, IL-22 induced expression of host defense genes (such as REG1A, REG1B, and DMBT1) in enterocytes, goblet cells, Paneth cells, Tuft cells, and even stem cells. Thus, IL-22 does not directly control the regenerative capacity of crypt stem cells but rather boosts Paneth cell numbers, as well as the expression of AMPs in all cell types.

Original language	English
Pages (from-to)	1333-1345.e6
Journal	Cell Stem Cell
Volume	29
Issue number	9
DOIs	https://doi.org/10.1016/j.stem.2022.08.002
Publication status	Published - 1 Sept 2022

Keywords

Calcium-Binding Proteins/metabolism
DNA-Binding Proteins/metabolism
Humans
Interleukins/metabolism
Intestinal Mucosa/metabolism
Intestine, Small/metabolism
Organoids/metabolism
Paneth Cells
Tumor Suppressor Proteins/metabolism

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10.1016/j.stem.2022.08.002

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He, G. W., Lin, L., DeMartino, J., Zheng, X., Staliarova, N., Dayton, T., Begthel, H., van de Wetering, W. J., Bodewes, E., van Zon, J., Tans, S., Lopez-Iglesias, C., Peters, P. J., Wu, W., Kotlarz, D., Klein, C., Margaritis, T., Holstege, F., & Clevers, H. (2022). Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation. Cell Stem Cell, 29(9), 1333-1345.e6. https://doi.org/10.1016/j.stem.2022.08.002

@article{515f46e06f3948529b35f2ba9eef81b1,

title = "Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation",

abstract = "Opposing roles have been proposed for IL-22 in intestinal pathophysiology. We have optimized human small intestinal organoid (hSIO) culturing, constitutively generating all differentiated cell types while maintaining an active stem cell compartment. IL-22 does not promote the expansion of stem cells but rather slows the growth of hSIOs. In hSIOs, IL-22 is required for formation of Paneth cells, the prime producers of intestinal antimicrobial peptides (AMPs). Introduction of inflammatory bowel disease (IBD)-associated loss-of-function mutations in the IL-22 co-receptor gene IL10RB resulted in abolishment of Paneth cells in hSIOs. Moreover, IL-22 induced expression of host defense genes (such as REG1A, REG1B, and DMBT1) in enterocytes, goblet cells, Paneth cells, Tuft cells, and even stem cells. Thus, IL-22 does not directly control the regenerative capacity of crypt stem cells but rather boosts Paneth cell numbers, as well as the expression of AMPs in all cell types.",

keywords = "Calcium-Binding Proteins/metabolism, DNA-Binding Proteins/metabolism, Humans, Interleukins/metabolism, Intestinal Mucosa/metabolism, Intestine, Small/metabolism, Organoids/metabolism, Paneth Cells, Tumor Suppressor Proteins/metabolism",

author = "He, {Gui Wei} and Lin Lin and Jeff DeMartino and Xuan Zheng and Nadzeya Staliarova and Talya Dayton and Harry Begthel and {van de Wetering}, {Willine J.} and Eduard Bodewes and {van Zon}, Jeroen and Sander Tans and Carmen Lopez-Iglesias and Peters, {Peter J.} and Wei Wu and Daniel Kotlarz and Christoph Klein and Thanasis Margaritis and Frank Holstege and Hans Clevers",

year = "2022",

month = sep,

day = "1",

doi = "10.1016/j.stem.2022.08.002",

language = "English",

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journal = "Cell Stem Cell",

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He, GW, Lin, L, DeMartino, J, Zheng, X, Staliarova, N, Dayton, T, Begthel, H, van de Wetering, WJ, Bodewes, E, van Zon, J, Tans, S, Lopez-Iglesias, C, Peters, PJ, Wu, W, Kotlarz, D, Klein, C, Margaritis, T, Holstege, F & Clevers, H 2022, 'Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation', Cell Stem Cell, vol. 29, no. 9, pp. 1333-1345.e6. https://doi.org/10.1016/j.stem.2022.08.002

TY - JOUR

T1 - Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

AU - He, Gui Wei

AU - Lin, Lin

AU - DeMartino, Jeff

AU - Zheng, Xuan

AU - Staliarova, Nadzeya

AU - Dayton, Talya

AU - Begthel, Harry

AU - van de Wetering, Willine J.

AU - Bodewes, Eduard

AU - van Zon, Jeroen

AU - Tans, Sander

AU - Lopez-Iglesias, Carmen

AU - Peters, Peter J.

AU - Wu, Wei

AU - Kotlarz, Daniel

AU - Klein, Christoph

AU - Margaritis, Thanasis

AU - Holstege, Frank

AU - Clevers, Hans

PY - 2022/9/1

Y1 - 2022/9/1

N2 - Opposing roles have been proposed for IL-22 in intestinal pathophysiology. We have optimized human small intestinal organoid (hSIO) culturing, constitutively generating all differentiated cell types while maintaining an active stem cell compartment. IL-22 does not promote the expansion of stem cells but rather slows the growth of hSIOs. In hSIOs, IL-22 is required for formation of Paneth cells, the prime producers of intestinal antimicrobial peptides (AMPs). Introduction of inflammatory bowel disease (IBD)-associated loss-of-function mutations in the IL-22 co-receptor gene IL10RB resulted in abolishment of Paneth cells in hSIOs. Moreover, IL-22 induced expression of host defense genes (such as REG1A, REG1B, and DMBT1) in enterocytes, goblet cells, Paneth cells, Tuft cells, and even stem cells. Thus, IL-22 does not directly control the regenerative capacity of crypt stem cells but rather boosts Paneth cell numbers, as well as the expression of AMPs in all cell types.

AB - Opposing roles have been proposed for IL-22 in intestinal pathophysiology. We have optimized human small intestinal organoid (hSIO) culturing, constitutively generating all differentiated cell types while maintaining an active stem cell compartment. IL-22 does not promote the expansion of stem cells but rather slows the growth of hSIOs. In hSIOs, IL-22 is required for formation of Paneth cells, the prime producers of intestinal antimicrobial peptides (AMPs). Introduction of inflammatory bowel disease (IBD)-associated loss-of-function mutations in the IL-22 co-receptor gene IL10RB resulted in abolishment of Paneth cells in hSIOs. Moreover, IL-22 induced expression of host defense genes (such as REG1A, REG1B, and DMBT1) in enterocytes, goblet cells, Paneth cells, Tuft cells, and even stem cells. Thus, IL-22 does not directly control the regenerative capacity of crypt stem cells but rather boosts Paneth cell numbers, as well as the expression of AMPs in all cell types.

KW - Calcium-Binding Proteins/metabolism

KW - DNA-Binding Proteins/metabolism

KW - Humans

KW - Interleukins/metabolism

KW - Intestinal Mucosa/metabolism

KW - Intestine, Small/metabolism

KW - Organoids/metabolism

KW - Paneth Cells

KW - Tumor Suppressor Proteins/metabolism

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U2 - 10.1016/j.stem.2022.08.002

DO - 10.1016/j.stem.2022.08.002

M3 - Article

C2 - 36002022

AN - SCOPUS:85136570527

SN - 1934-5909

VL - 29

SP - 1333-1345.e6

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 9

ER -

Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

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Keywords

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