ArticleProceedings of the National Academy of Sciences of the United States of America2016
Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
What it found
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Who cites it
191 citing papers in PubMed, 297 citations in OpenAlex.
- Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease.The Journal of clinical investigation · 2018Trial
- Westernized diet related arachidonic acid metabolism expands DNA error-prone growth factor-dependent colonic quiescent stem cells in adolescent mice.Cell death & disease · 2026Article
- Intestinal Epithelial MHC-II at the Interface of Microbiota, Immunity, and Inflammation.International journal of molecular sciences · 2026Review
- Recent advancements and limitations of intestinal organoids for clinical applications.Progress in biomedical engineering (Bristol, England) · 2026Review
- Review
- CBP phosphorylation maintains intestinal homeostasis by supporting the stem cell niche through versican.Nature communications · 2026Article
- Progress in human intestinal organoid research: applications to acute gastroenteritis viruses.Stem cell research & therapy · 2026Review
- A Rare T-Cell Factor 4 Lineage-negative Epithelial Stem Cell Supports Wound Repair and APC-deletion-induced Colon Tumorigenesis.bioRxiv : the preprint server for biology · 2026Article
- Cold Exposure Alleviates Colitis via Parallel Integration of Colonic Mucosal Regeneration and Ileal Antimicrobial Defense.Biomedicines · 2026Article
- Colitis-Associated Carcinoma: The Quintessential Epithelial Neoplasia Driven by Chronic Inflammation.Cells · 2026Review
- Pooled single-cell screen in colorectal cancer defines transcriptional modules linked to oncogenes.Molecular systems biology · 2026Article
- Stem Cell Therapy for Inflammatory Diseases: Progress, Challenges, and Future Directions.MedComm · 2026Review
- Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer.Cancer cell · 2026Article
- Observational
- The Intestinal Barrier: A Multilayered Gatekeeper Against Systemic Disease.International journal of microbiology · 2026Review
- A human intestinal epithelial-mesenchyme-immune triple culture system for disease modelling.Frontiers in cell and developmental biology · 2026Article
- Advancing Esophageal Disease Modeling: Microfluidic Platforms for Adult Tissue-Resident Stem Cell Culture and Differentiation.Gastro hep advances · 2026Article
- REG/Reg family proteins: mediating gut microbiota homeostasis and implications in digestive diseases.Gut microbes · 2025Review
- Intestinal Goblet Cell-Expressed Reg4 Ameliorates Intestinal Inflammation Potentially by Restraining Pathogenic Escherichia coli Infection.Probiotics and antimicrobial proteins · 2025Article
- Identification of tumor initiating cells and early marker genes in normal colonic epithelium that lead to neoplastic transformation.Research square · 2025Article
131 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
Leucine-rich repeat-containing G-protein coupled receptor 5-positive (Lgr5(+)) stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF, and Notch signals to neighboring Lgr5(+) stem cells. Whereas the colon lacks Paneth cells, deep crypt secretory (DCS) cells are intermingled with Lgr5(+) stem cells at crypt bottoms. Here, we report regenerating islet-derived family member 4 (Reg4) as a marker of DCS cells. To investigate a niche function, we eliminated DCS cells by using the diphtheria-toxin receptor gene knocked into the murine Reg4 locus. Ablation of DCS cells results in loss of stem cells from colonic crypts and disrupts gut homeostasis and colon organoid growth. In agreement, sorted Reg4(+) DCS cells promote organoid formation of single Lgr5(+) colon stem cells. DCS cells can be massively produced from Lgr5(+) colon stem cells in vitro by combined Notch inhibition and Wnt activation. We conclude that Reg4(+) DCS cells serve as Paneth cell equivalents in the colon crypt niche.
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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.