Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec 1;325(6):G493-G500.
doi: 10.1152/ajpgi.00093.2023. Epub 2023 Sep 12.

The emerging roles of deep crypt secretory cells in colonic physiology

Michael A Schumacher  1   2
Affiliations
Review

The emerging roles of deep crypt secretory cells in colonic physiology

Michael A Schumacher. Am J Physiol Gastrointest Liver Physiol. .

Abstract

Deep crypt secretory (DCS) cells are a population of epithelial cells located at the colonic crypt base that share some similarities to Paneth and goblet cells. They were initially defined as c-Kit expressing cells, though subsequent work showed that they are more specifically marked by Reg4 in the murine colon. The best-understood function of DCS cells at present is supporting the stem cell niche by generating Notch and EGF ligands. However, as these cells also express immunoregulatory (e.g., Ccl6) and host defense (e.g., Retnlb) genes, it is likely they have additional functions in maintaining colonic health outside of maintenance of the stem niche. Recent advances in single-cell transcriptomic profiling hint at additional epithelial and immune roles that may exist for these cells and have aided in elucidating their developmental lineage. This review highlights the emerging evidence supporting a crucial role for DCS cells in intestinal physiology, the current understanding of how these cells are regulated, and their potential role(s) in colonic disease.

Keywords: IBD; colon; epithelium; secretory cells.

PubMed Disclaimer

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Figure 1.
Figure 1.
The role and regulation of deep crypt secretory (DCS) cells in the colon. Localized tissue signaling pathways (Wnt, Notch) and cytokines (IL-13) regulate the DCS cell population size. DCS cells secrete stem support factors and host defense factors (RELMβ, CCL6) to maintain tissue homeostasis. +A driver of DCS cell differentiation.
Figure 2.
Figure 2.
Analysis of Reg4-expressing deep crypt secretory (DCS) cells along the length of the murine colon. Swiss-rolled colons of formaldehyde-fixed and paraffin-embedded sections from wild-type mice were analyzed by RNAScope for the DCS cell marker, Reg4 (Probe no. 409601; Advanced Cell Diagnostics). Regionally collected colonic biopsies from the proximal colon (PC) to distal colon (DC) were analyzed by quantitative PCR for Reg4 (TaqMan assay Mm00471115_m1; Thermo Fisher). Animal use was approved and monitored by the Children’s Hospital Los Angeles Institutional Animal Care and Use Committee (Animal Welfare Assurance A3276-01).
Figure 3.
Figure 3.
REG4 and SPINK4 are elevated in ulcerative colitis datasets. Previously generated ulcerative colitis (UC) patient datasets were analyzed for expression of murine deep crypt secretory (DCS) cell markers REG4 and SPINK4. GDS4519 contains patients with UC and non-UC monozygotic twin controls (CON). GDS4365 contains patients with UC and non-UC controls (CON). Both datasets were generated from individuals who gave written informed consent (59, 60). **P < 0.01, ***P < 0.001 ****P < 0.0001.
See this image and copyright information in PMC

References

    1. Cheng H, Leblond CP. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine V. Unitarian theory of the origin of the four epithelial cell types. Am J Anat 141: 537–561, 1974. doi:10.1002/aja.1001410407. - DOI - PubMed
    1. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449: 1003–1007, 2007. doi:10.1038/nature06196. - DOI - PubMed
    1. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469: 415–418, 2011. doi:10.1038/nature09637. - DOI - PMC - PubMed
    1. Tanaka M, Saito H, Kusumi T, Fukuda S, Shimoyama T, Sasaki Y, Suto K, Munakata A, Kudo H. Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease. J Gastroenterol Hepatol 16: 1353–1359, 2001. doi:10.1046/j.1440-1746.2001.02629.x. - DOI - PubMed
    1. Puiman PJ, Burger-Van Paassen N, Schaart MW, De Bruijn ACJM, De Krijger RR, Tibboel D, Van Goudoever JB, Renes IB. Paneth cell hyperplasia and metaplasia in necrotizing enterocolitis. Pediatr Res 69: 217–223, 2011. doi:10.1203/PDR.0b013e3182092a9a. - DOI - PubMed

Publication types

LinkOut - more resources