High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Joep Beumer; Jens Puschhof; Julia Bauzá-Martinez; Adriana Martínez-Silgado; Rasa Elmentaite; Kylie R James; Alexander Ross; Delilah Hendriks; Benedetta Artegiani; Georg A Busslinger; Bas Ponsioen; Amanda Andersson-Rolf; Aurelia Saftien; Charelle Boot; Kai Kretzschmar; Maarten H Geurts; Yotam E Bar-Ephraim; Cayetano Pleguezuelos-Manzano; Yorick Post; Harry Begthel; Franka van der Linden; Carmen Lopez-Iglesias; Willine J van de Wetering; Reinier van der Linden; Peter J Peters; Albert J R Heck; Joachim Goedhart; Hugo Snippert; Matthias Zilbauer; Sarah A Teichmann; Wei Wu; Hans Clevers

doi:10.1016/j.cell.2020.04.036

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Joep Beumer, Jens Puschhof, Julia Bauzá-Martinez, Adriana Martínez-Silgado, Rasa Elmentaite, Kylie R James, Alexander Ross, Delilah Hendriks, Benedetta Artegiani, Georg A Busslinger, Bas Ponsioen, Amanda Andersson-Rolf, Aurelia Saftien, Charelle Boot, Kai Kretzschmar, Maarten H Geurts, Yotam E Bar-Ephraim, Cayetano Pleguezuelos-Manzano, Yorick Post, Harry BegthelFranka van der Linden, Carmen Lopez-Iglesias, Willine J van de Wetering, Reinier van der Linden, Peter J Peters, Albert J R Heck, Joachim Goedhart, Hugo Snippert, Matthias Zilbauer, Sarah A Teichmann, Wei Wu, Hans Clevers

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.

Originele taal-2	Engels
Pagina's (van-tot)	1291-1306.e19
Tijdschrift	Cell
Volume	181
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1016/j.cell.2020.04.036
Status	Gepubliceerd - 11 jun. 2020

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10.1016/j.cell.2020.04.036

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Beumer, J., Puschhof, J., Bauzá-Martinez, J., Martínez-Silgado, A., Elmentaite, R., James, K. R., Ross, A., Hendriks, D., Artegiani, B., Busslinger, G. A., Ponsioen, B., Andersson-Rolf, A., Saftien, A., Boot, C., Kretzschmar, K., Geurts, M. H., Bar-Ephraim, Y. E., Pleguezuelos-Manzano, C., Post, Y., ... Clevers, H. (2020). High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells. Cell, 181(6), 1291-1306.e19. https://doi.org/10.1016/j.cell.2020.04.036

@article{73363b0c842547f7bb5962156970642e,

title = "High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells",

abstract = "Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.",

author = "Joep Beumer and Jens Puschhof and Julia Bauz{\'a}-Martinez and Adriana Mart{\'i}nez-Silgado and Rasa Elmentaite and James, {Kylie R} and Alexander Ross and Delilah Hendriks and Benedetta Artegiani and Busslinger, {Georg A} and Bas Ponsioen and Amanda Andersson-Rolf and Aurelia Saftien and Charelle Boot and Kai Kretzschmar and Geurts, {Maarten H} and Bar-Ephraim, {Yotam E} and Cayetano Pleguezuelos-Manzano and Yorick Post and Harry Begthel and {van der Linden}, Franka and Carmen Lopez-Iglesias and {van de Wetering}, {Willine J} and {van der Linden}, Reinier and Peters, {Peter J} and Heck, {Albert J R} and Joachim Goedhart and Hugo Snippert and Matthias Zilbauer and Teichmann, {Sarah A} and Wei Wu and Hans Clevers",

year = "2020",

month = jun,

day = "11",

doi = "10.1016/j.cell.2020.04.036",

language = "English",

volume = "181",

pages = "1291--1306.e19",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "6",

}

Beumer, J, Puschhof, J, Bauzá-Martinez, J, Martínez-Silgado, A, Elmentaite, R, James, KR, Ross, A, Hendriks, D, Artegiani, B, Busslinger, GA, Ponsioen, B, Andersson-Rolf, A, Saftien, A, Boot, C, Kretzschmar, K, Geurts, MH, Bar-Ephraim, YE, Pleguezuelos-Manzano, C, Post, Y, Begthel, H, van der Linden, F, Lopez-Iglesias, C, van de Wetering, WJ, van der Linden, R, Peters, PJ, Heck, AJR, Goedhart, J, Snippert, H, Zilbauer, M, Teichmann, SA, Wu, W & Clevers, H 2020, 'High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells', Cell, vol. 181, nr. 6, blz. 1291-1306.e19. https://doi.org/10.1016/j.cell.2020.04.036

TY - JOUR

T1 - High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

AU - Beumer, Joep

AU - Puschhof, Jens

AU - Bauzá-Martinez, Julia

AU - Martínez-Silgado, Adriana

AU - Elmentaite, Rasa

AU - James, Kylie R

AU - Ross, Alexander

AU - Hendriks, Delilah

AU - Artegiani, Benedetta

AU - Busslinger, Georg A

AU - Ponsioen, Bas

AU - Andersson-Rolf, Amanda

AU - Saftien, Aurelia

AU - Boot, Charelle

AU - Kretzschmar, Kai

AU - Geurts, Maarten H

AU - Bar-Ephraim, Yotam E

AU - Pleguezuelos-Manzano, Cayetano

AU - Post, Yorick

AU - Begthel, Harry

AU - van der Linden, Franka

AU - Lopez-Iglesias, Carmen

AU - van de Wetering, Willine J

AU - van der Linden, Reinier

AU - Peters, Peter J

AU - Heck, Albert J R

AU - Goedhart, Joachim

AU - Snippert, Hugo

AU - Zilbauer, Matthias

AU - Teichmann, Sarah A

AU - Wu, Wei

AU - Clevers, Hans

PY - 2020/6/11

Y1 - 2020/6/11

N2 - Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.

AB - Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.

U2 - 10.1016/j.cell.2020.04.036

DO - 10.1016/j.cell.2020.04.036

M3 - Article

C2 - 32407674

SN - 0092-8674

VL - 181

SP - 1291-1306.e19

JO - Cell

JF - Cell

IS - 6

ER -

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

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