ArticleCell stem cell2017
Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells.
Article in Cell stem cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers.
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Who cites it
238 citing papers in PubMed, 362 citations in OpenAlex.
- Human Small Intestinal Organoids Differentiation Protocols Towards All Mature Epithelial Lineages.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Updated Protocols for 3D and 2D Culture and Histological Analysis of Intestinal Organoids.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Whole-Mount Immunostaining of Human Intestinal Organoids.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Review
- Proliferation and differentiation in intestinal organoids are balanced by ligand-modulated EGFR trafficking.Life science alliance · 2026Article
- Bacterial serine protease EspP induces differentiation and expansion of enteroendocrine cells in human colonoids.Physiological genomics · 2026Article
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- Quantitative imaging of dynamic processes in intestinal organoids.Nature protocols · 2026Review
- Porcine intestinal goblet cells: Guardians of mucosal immunity and barrier function.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- Melatonin-inspired hybrid spheroids accelerate intestinal repair via YAP-driven fetal reprogramming.Asian journal of pharmaceutical sciences · 2026Article
- Multiomic analyses delineate human neuroendocrine tumor cell states in relation to normal enteroendocrine cell ontogeny.The Journal of clinical investigation · 2026Article
- JAK inhibitors alleviate EGFR-inhibitor-induced diarrhea by protecting intestinal stem cells from adaptive-immune-exacerbated injury.Nature communications · 2026Article
- Preservation of Human Colonic Stem Cells Requires an ERK Dynamics Checkpoint Mediated by AKT.bioRxiv : the preprint server for biology · 2026Article
- Characterization of jejunal enteroids in human obesity; a model for studying GLP-1 cells.International journal of obesity (2005) · 2026Article
- Efficient control of enterochromaffin versus islet differentiation from human pluripotent stem cell-derived pancreatic progenitors.Nature communications · 2026Article
- Intestinal organoid screen reveals that Bacillus velezensis PGM541 promotes epithelial proliferation via its metabolite butyric acid.Microbiome · 2026Article
- Engineered intestinal crypt geometry uncovers YAP1-dependent fetal-to-adult transition.Cell stem cell · 2026Article
- Single-nucleus multi-omics analysis of mouse small-intestinal Lgr5+ cell populations reveals Foxa3-induced Paneth cell-lineage differentiation.Communications biology · 2026Article
- Obesity impairs gut repair via AFABP-mediated iron overload in intestinal stem cells.Nature metabolism · 2026Article
178 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lgr5+ adult intestinal stem cells are highly proliferative throughout life. Single Lgr5+ stem cells can be cultured into three-dimensional organoids containing all intestinal epithelial cell types at near-normal ratios. Conditions to generate the main cell types (enterocyte, goblet cells, Paneth cells, and M cells) are well established, but signals to induce the spectrum of hormone-producing enteroendocrine cells (EECs) have remained elusive. Here, we induce Lgr5+ stem cell quiescence in vitro by blocking epidermal growth factor receptor (EGFR) or mitogen-associated protein kinase (MAPK) signaling pathways in organoids and show that their quiescent state is readily reverted. Quiescent Lgr5+ stem cells acquire a distinct molecular signature biased toward EEC differentiation. Indeed, combined inhibition of Wnt, Notch, and MAPK pathways efficiently generates a diversity of EEC hormone-expressing subtypes in vitro. Our observations uncouple Wnt-dependent stem cell maintenance from EGF-dependent proliferation and provide an approach for the study of the elusive EECs in a defined environment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.