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. 2017 Sep;3(3):143-148.
doi: 10.1007/s40610-017-0065-7. Epub 2017 Jul 13.

Recent Advances in Intestinal Stem Cells

Affiliations

Recent Advances in Intestinal Stem Cells

Laura R McCabe et al. Curr Mol Biol Rep. 2017 Sep.

Abstract

Purpose of review: The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here.

Recent findings: The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and myofibroblast cells secrete factors that regulate ISC proliferation. Finally, several studies indicate that the microbiome metabolites regulate ISC growth.

Summary: ISC cells can be plastic and integrate a complexity of environmental/niche cues to trigger or suppress proliferation as needed.

Keywords: Bmi1+; CBC; Lrg5+; Wnt; intestine; stem cell.

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Conflict of interest statement

Conflict of Interest Laura McCabe reports grants from National Institute of Health RO1 DK101050, grants from National Institute of Health RO1 AT007695, during the conduct of the study. Narayanan Parameswaran reports grants from National Institutes of Health during the conduct of the study.

Figures

Figure 1
Figure 1
Model of the small intestinal cell organization in the crypt and villus region. Key ISC cells are the CBC (green cells in crypt) and the +4 position cells (in purple). TA progenitor cells are tan. Cells of the ISC niche (noted by blue letters) include paneth (orange), immune cells (yellow) and myofibroblasts (blue). The microbiome is also thought to influence the ISC. Note that the colon structure (not shown) does not include villi or Paneth cells, although there are Paneth-like cells present in the colon crypts.
Figure 2
Figure 2
Model of ISC regulation in the crypt region. A variety of signals regulate stem cell proliferation. Many signals (noted in boxes – green = simulate while red = decrease) are from the ISC niche which is composed of myofibroblasts (blue), paneth cells (orange), and immune cells (yellow). The microbiome is also thought to contribute to ISC regulation. Several signaling pathways promote growth and their suppression is important for differentiation. Similarly, factors that suppress growth are found to be at higher levels in the villus compared with the crypt region. Overall, factors that stimulate ISC proliferation include Wnt, EGF, Noggin, R-spondin. Factors that reduce ISC proliferation include BMP signaling and miR375.

References

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