Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models

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

Standard

Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models. / Beumer, Joep; Bauzá-Martinez, Julia; Veth, Tim S.; Geurts, Veerle; Boot, Charelle; Gilliam-Vigh, Hannah; Poulsen, Steen S.; Knop, Filip K.; Wu, Wei; Clevers, Hans.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 46, e2212057119, 2022.

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

Harvard

Beumer, J, Bauzá-Martinez, J, Veth, TS, Geurts, V, Boot, C, Gilliam-Vigh, H, Poulsen, SS, Knop, FK, Wu, W & Clevers, H 2022, 'Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 46, e2212057119. https://doi.org/10.1073/pnas.2212057119

APA

Beumer, J., Bauzá-Martinez, J., Veth, T. S., Geurts, V., Boot, C., Gilliam-Vigh, H., Poulsen, S. S., Knop, F. K., Wu, W., & Clevers, H. (2022). Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models. Proceedings of the National Academy of Sciences of the United States of America, 119(46), [e2212057119]. https://doi.org/10.1073/pnas.2212057119

Vancouver

Beumer J, Bauzá-Martinez J, Veth TS, Geurts V, Boot C, Gilliam-Vigh H et al. Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(46). e2212057119. https://doi.org/10.1073/pnas.2212057119

Author

Beumer, Joep ; Bauzá-Martinez, Julia ; Veth, Tim S. ; Geurts, Veerle ; Boot, Charelle ; Gilliam-Vigh, Hannah ; Poulsen, Steen S. ; Knop, Filip K. ; Wu, Wei ; Clevers, Hans. / Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models. In: Proceedings of the National Academy of Sciences of the United States of America. 2022 ; Vol. 119, No. 46.

Bibtex

@article{12056280ce1c480985268c1e99d3f432,
title = "Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models",
abstract = "Enteroendocrine cells (EECs) secrete hormones in response to ingested nutrients to control physiological processes such as appetite and insulin release. EEC hormones are synthesized as large proproteins that undergo proteolytic processing to generate bioactive peptides. Mutations in EEC-enriched proteases are associated with endocrinopathies. Due to the relative rarity of EECs and a paucity of in vitro models, intestinal prohormone processing remains challenging to assess. Here, human gut organoids in which EECs can efficiently be induced are subjected to CRISPR-Cas9-mediated modification of EEC-expressed endopeptidase and exopeptidase genes. We employ mass spectrometry-based analyses to monitor peptide processing and identify glucagon production in intestinal EECs, stimulated upon bone morphogenic protein (BMP) signaling. We map the substrates and products of major EECs endo- and exopeptidases. Our studies provide a comprehensive description of peptide hormones produced by human EECs and define the roles of specific proteases in their generation.",
keywords = "CRISPR-Cas9, enteroendocrine cells, intestinal organoids, peptidomics, prohormone processing",
author = "Joep Beumer and Julia Bauz{\'a}-Martinez and Veth, {Tim S.} and Veerle Geurts and Charelle Boot and Hannah Gilliam-Vigh and Poulsen, {Steen S.} and Knop, {Filip K.} and Wei Wu and Hans Clevers",
year = "2022",
doi = "10.1073/pnas.2212057119",
language = "English",
volume = "119",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "46",

}

RIS

TY - JOUR

T1 - Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models

AU - Beumer, Joep

AU - Bauzá-Martinez, Julia

AU - Veth, Tim S.

AU - Geurts, Veerle

AU - Boot, Charelle

AU - Gilliam-Vigh, Hannah

AU - Poulsen, Steen S.

AU - Knop, Filip K.

AU - Wu, Wei

AU - Clevers, Hans

PY - 2022

Y1 - 2022

N2 - Enteroendocrine cells (EECs) secrete hormones in response to ingested nutrients to control physiological processes such as appetite and insulin release. EEC hormones are synthesized as large proproteins that undergo proteolytic processing to generate bioactive peptides. Mutations in EEC-enriched proteases are associated with endocrinopathies. Due to the relative rarity of EECs and a paucity of in vitro models, intestinal prohormone processing remains challenging to assess. Here, human gut organoids in which EECs can efficiently be induced are subjected to CRISPR-Cas9-mediated modification of EEC-expressed endopeptidase and exopeptidase genes. We employ mass spectrometry-based analyses to monitor peptide processing and identify glucagon production in intestinal EECs, stimulated upon bone morphogenic protein (BMP) signaling. We map the substrates and products of major EECs endo- and exopeptidases. Our studies provide a comprehensive description of peptide hormones produced by human EECs and define the roles of specific proteases in their generation.

AB - Enteroendocrine cells (EECs) secrete hormones in response to ingested nutrients to control physiological processes such as appetite and insulin release. EEC hormones are synthesized as large proproteins that undergo proteolytic processing to generate bioactive peptides. Mutations in EEC-enriched proteases are associated with endocrinopathies. Due to the relative rarity of EECs and a paucity of in vitro models, intestinal prohormone processing remains challenging to assess. Here, human gut organoids in which EECs can efficiently be induced are subjected to CRISPR-Cas9-mediated modification of EEC-expressed endopeptidase and exopeptidase genes. We employ mass spectrometry-based analyses to monitor peptide processing and identify glucagon production in intestinal EECs, stimulated upon bone morphogenic protein (BMP) signaling. We map the substrates and products of major EECs endo- and exopeptidases. Our studies provide a comprehensive description of peptide hormones produced by human EECs and define the roles of specific proteases in their generation.

KW - CRISPR-Cas9

KW - enteroendocrine cells

KW - intestinal organoids

KW - peptidomics

KW - prohormone processing

UR - http://www.scopus.com/inward/record.url?scp=85141346727&partnerID=8YFLogxK

U2 - 10.1073/pnas.2212057119

DO - 10.1073/pnas.2212057119

M3 - Journal article

C2 - 36343264

AN - SCOPUS:85141346727

VL - 119

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 46

M1 - e2212057119

ER -

ID: 327063948