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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.

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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.
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