Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells

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Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells. / V. Grunddal, Kaare; Tonack, Sarah; Egerod, Kristoffer L.; Thompson, Jonathan James; Petersen, Natalia; Engelstoft, Maja S.; Vagne, Constance; Keinse, Celine; Gradwohl, Gerard; Offermanns, Stefan; Schwartz, Thue W.

In: Molecular Metabolism, Vol. 51, 101231, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

V. Grunddal, K, Tonack, S, Egerod, KL, Thompson, JJ, Petersen, N, Engelstoft, MS, Vagne, C, Keinse, C, Gradwohl, G, Offermanns, S & Schwartz, TW 2021, 'Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells', Molecular Metabolism, vol. 51, 101231. https://doi.org/10.1016/j.molmet.2021.101231

APA

V. Grunddal, K., Tonack, S., Egerod, K. L., Thompson, J. J., Petersen, N., Engelstoft, M. S., Vagne, C., Keinse, C., Gradwohl, G., Offermanns, S., & Schwartz, T. W. (2021). Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells. Molecular Metabolism, 51, [101231]. https://doi.org/10.1016/j.molmet.2021.101231

Vancouver

V. Grunddal K, Tonack S, Egerod KL, Thompson JJ, Petersen N, Engelstoft MS et al. Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells. Molecular Metabolism. 2021;51. 101231. https://doi.org/10.1016/j.molmet.2021.101231

Author

V. Grunddal, Kaare ; Tonack, Sarah ; Egerod, Kristoffer L. ; Thompson, Jonathan James ; Petersen, Natalia ; Engelstoft, Maja S. ; Vagne, Constance ; Keinse, Celine ; Gradwohl, Gerard ; Offermanns, Stefan ; Schwartz, Thue W. / Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells. In: Molecular Metabolism. 2021 ; Vol. 51.

Bibtex

@article{632416f1cb18412b9c66ffd32a235631,
title = "Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells",
abstract = "Objective: GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known to be mainly expressed in the parathyroid gland and epididymis. This investigation aimed to delineate the cellular expression of GPR64 throughout the body with focus on the gastrointestinal (GI) tract. Methods: Transgenic Gpr64mCherry reporter mice were histologically examined throughout the body and reporter protein expression in intestinal tuft cells was confirmed by specific cell ablation. The GPCR repertoire of intestinal Gpr64mCherry-positive tuft cells was analyzed by quantitative RT-PCR analysis and in situ hybridization. The Gpr64mCherry was crossed into the general tuft cell reporter Trpm5GFP to generate small intestinal organoids for time-lapse imaging. Intestinal tuft cells were isolated from small intestine, FACS-purified and transcriptionally compared using RNAseq analysis. Results: Expression of the Gpr64mCherry reporter was identified in multiple organs and specifically in olfactory microvillous cells, enteric nerves, and importantly in respiratory and GI tuft cells. In the small intestine, cell ablation targeting Gpr64-expressing epithelial cells eliminated tuft cells. Transcriptional analysis of small intestinal Gpr64mCherry -positive tuft cells confirmed expression of Gpr64 and the chemo-sensors Sucnr1, Gprc5c, Drd3, and Gpr41/Ffar3. Time-lapse studies of organoids from Trpm5GFP:Gpr64mCherry mice revealed sequential expression of initially Trpm5GFP and subsequently also Gpr64mCherry in maturing intestinal tuft cells. RNA-seq analysis of small intestinal tuft cells based on these two markers demonstrated a dynamic change in expression of transcription factors and GPCRs from young to mature tuft cells. Conclusions: GPR64 is expressed in chemosensory epithelial cells across a broad range of tissues; however, in the GI tract, GPR64 is remarkably selectively expressed in mature versus young immunoregulatory tuft cells. (c) 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).",
keywords = "ADGRG2, GPR64, GPCRs, Tuft cells, Chemosensory cells, CHAIN FATTY-ACIDS, BRUSH CELLS, G-PROTEIN, GUT MICROBIOTA, STEM-CELLS, CHEMOSENSORY CELLS, MUCOSAL IMMUNITY, TYPE-2 IMMUNITY, IN-VITRO, L-DOPA",
author = "{V. Grunddal}, Kaare and Sarah Tonack and Egerod, {Kristoffer L.} and Thompson, {Jonathan James} and Natalia Petersen and Engelstoft, {Maja S.} and Constance Vagne and Celine Keinse and Gerard Gradwohl and Stefan Offermanns and Schwartz, {Thue W.}",
year = "2021",
doi = "10.1016/j.molmet.2021.101231",
language = "English",
volume = "51",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft cells

AU - V. Grunddal, Kaare

AU - Tonack, Sarah

AU - Egerod, Kristoffer L.

AU - Thompson, Jonathan James

AU - Petersen, Natalia

AU - Engelstoft, Maja S.

AU - Vagne, Constance

AU - Keinse, Celine

AU - Gradwohl, Gerard

AU - Offermanns, Stefan

AU - Schwartz, Thue W.

PY - 2021

Y1 - 2021

N2 - Objective: GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known to be mainly expressed in the parathyroid gland and epididymis. This investigation aimed to delineate the cellular expression of GPR64 throughout the body with focus on the gastrointestinal (GI) tract. Methods: Transgenic Gpr64mCherry reporter mice were histologically examined throughout the body and reporter protein expression in intestinal tuft cells was confirmed by specific cell ablation. The GPCR repertoire of intestinal Gpr64mCherry-positive tuft cells was analyzed by quantitative RT-PCR analysis and in situ hybridization. The Gpr64mCherry was crossed into the general tuft cell reporter Trpm5GFP to generate small intestinal organoids for time-lapse imaging. Intestinal tuft cells were isolated from small intestine, FACS-purified and transcriptionally compared using RNAseq analysis. Results: Expression of the Gpr64mCherry reporter was identified in multiple organs and specifically in olfactory microvillous cells, enteric nerves, and importantly in respiratory and GI tuft cells. In the small intestine, cell ablation targeting Gpr64-expressing epithelial cells eliminated tuft cells. Transcriptional analysis of small intestinal Gpr64mCherry -positive tuft cells confirmed expression of Gpr64 and the chemo-sensors Sucnr1, Gprc5c, Drd3, and Gpr41/Ffar3. Time-lapse studies of organoids from Trpm5GFP:Gpr64mCherry mice revealed sequential expression of initially Trpm5GFP and subsequently also Gpr64mCherry in maturing intestinal tuft cells. RNA-seq analysis of small intestinal tuft cells based on these two markers demonstrated a dynamic change in expression of transcription factors and GPCRs from young to mature tuft cells. Conclusions: GPR64 is expressed in chemosensory epithelial cells across a broad range of tissues; however, in the GI tract, GPR64 is remarkably selectively expressed in mature versus young immunoregulatory tuft cells. (c) 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

AB - Objective: GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known to be mainly expressed in the parathyroid gland and epididymis. This investigation aimed to delineate the cellular expression of GPR64 throughout the body with focus on the gastrointestinal (GI) tract. Methods: Transgenic Gpr64mCherry reporter mice were histologically examined throughout the body and reporter protein expression in intestinal tuft cells was confirmed by specific cell ablation. The GPCR repertoire of intestinal Gpr64mCherry-positive tuft cells was analyzed by quantitative RT-PCR analysis and in situ hybridization. The Gpr64mCherry was crossed into the general tuft cell reporter Trpm5GFP to generate small intestinal organoids for time-lapse imaging. Intestinal tuft cells were isolated from small intestine, FACS-purified and transcriptionally compared using RNAseq analysis. Results: Expression of the Gpr64mCherry reporter was identified in multiple organs and specifically in olfactory microvillous cells, enteric nerves, and importantly in respiratory and GI tuft cells. In the small intestine, cell ablation targeting Gpr64-expressing epithelial cells eliminated tuft cells. Transcriptional analysis of small intestinal Gpr64mCherry -positive tuft cells confirmed expression of Gpr64 and the chemo-sensors Sucnr1, Gprc5c, Drd3, and Gpr41/Ffar3. Time-lapse studies of organoids from Trpm5GFP:Gpr64mCherry mice revealed sequential expression of initially Trpm5GFP and subsequently also Gpr64mCherry in maturing intestinal tuft cells. RNA-seq analysis of small intestinal tuft cells based on these two markers demonstrated a dynamic change in expression of transcription factors and GPCRs from young to mature tuft cells. Conclusions: GPR64 is expressed in chemosensory epithelial cells across a broad range of tissues; however, in the GI tract, GPR64 is remarkably selectively expressed in mature versus young immunoregulatory tuft cells. (c) 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

KW - ADGRG2

KW - GPR64

KW - GPCRs

KW - Tuft cells

KW - Chemosensory cells

KW - CHAIN FATTY-ACIDS

KW - BRUSH CELLS

KW - G-PROTEIN

KW - GUT MICROBIOTA

KW - STEM-CELLS

KW - CHEMOSENSORY CELLS

KW - MUCOSAL IMMUNITY

KW - TYPE-2 IMMUNITY

KW - IN-VITRO

KW - L-DOPA

U2 - 10.1016/j.molmet.2021.101231

DO - 10.1016/j.molmet.2021.101231

M3 - Journal article

C2 - 33831593

VL - 51

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

M1 - 101231

ER -

ID: 278486864