Dataset Information

EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids.

ABSTRACT: Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, and drug development. Here, we interrogated the cell signaling environment within the developing human intestine to identify niche cues that may be important for epithelial development and homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed in the developing human crypt. Enteroids generated from the developing human intestine grown in standard culture conditions, which contain EGF, are dominated by stem and progenitor cells and feature little differentiation and no spatial organization. Our results demonstrate that EREG can replace EGF in vitro, and EREG leads to spatially resolved enteroids that feature budded and proliferative crypt domains and a differentiated villus-like central lumen. Multiomic (transcriptome plus epigenome) profiling of native crypts, EGF-grown enteroids, and EREG-grown enteroids showed that EGF enteroids have an altered chromatin landscape that is dependent on EGF concentration, downregulate the master intestinal transcription factor CDX2, and ectopically express stomach genes, a phenomenon that is reversible. This is in contrast to EREG-grown enteroids, which remain intestine like in culture. Thus, EREG creates a homeostatic intestinal niche in vitro, enabling interrogation of stem cell function, cellular differentiation, and disease modeling.

SUBMITTER: Childs CJ

PROVIDER: S-EPMC10070114 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids.

Childs Charlie J CJ Holloway Emily M EM Sweet Caden W CW Tsai Yu-Hwai YH Wu Angeline A Vallie Abigail A Eiken Madeline K MK Capeling Meghan M MM Zwick Rachel K RK Palikuqi Brisa B Trentesaux Coralie C Wu Joshua H JH Pellón-Cardenas Oscar O Zhang Charles J CJ Glass Ian I Loebel Claudia C Yu Qianhui Q Camp J Gray JG Sexton Jonathan Z JZ Klein Ophir D OD Verzi Michael P MP Spence Jason R JR

JCI insight 20230322 6

Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, and drug development. Here, we interrogated the cell signaling environment within the developing human intestine to identify niche cues that may be important for epithelial development and homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed in the developing human crypt. ...[more]

PMID: 36821371

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Dataset Information

EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids.

Publications

EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids.

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