ArticleProceedings of the National Academy of Sciences of the United States of America2022
Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Multi-omics analysis of glycolytic reprogramming and ROS dynamics in host-specific responses to Salmonella Typhi infection in mice.Journal of advanced research · 2026Article
- Incretin hormones and obesity.The Journal of physiology · 2025Review
- Enteroendocrine cells: the gatekeepers of microbiome-gut-brain communication.NPJ biofilms and microbiomes · 2025Review
- Macrophage-augmented intestinal organoids model virus-host interactions in enteric viral diseases and facilitate therapeutic development.Nature communications · 2025Article
- Intestinal organoids in inflammatory bowel disease: advances, applications, and future directions.Frontiers in cell and developmental biology · 2025Review
- Type 1 diabetes human enteroid studies reveal major changes in the intestinal epithelial compartment.Scientific reports · 2024Article
- The intestine as an endocrine organ and the role of gut hormones in metabolic regulation.Nature reviews. Gastroenterology & hepatology · 2023Review
- 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 · 2022Article
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10 authors.
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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.
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