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
. 2022;13(3):843-856.
doi: 10.1016/j.jcmgh.2021.12.005. Epub 2021 Dec 13.

Injury-Induced Cellular Plasticity Drives Intestinal Regeneration

Anne R Meyer  1 , Monica E Brown  1 , Patrick S McGrath  1 , Peter J Dempsey  2
Affiliations
Review

Injury-Induced Cellular Plasticity Drives Intestinal Regeneration

Anne R Meyer et al. Cell Mol Gastroenterol Hepatol. 2022.

Abstract

The epithelial lining of the intestine, particularly the stem cell compartment, is affected by harsh conditions in the luminal environment and also is susceptible to genotoxic agents such as radiation and chemotherapy. Therefore, the ability for intestinal epithelial cells to revert to a stem cell state is an important physiological damage response to regenerate the intestinal epithelium at sites of mucosal injury. Many signaling networks involved in maintaining the stem cell niche are activated as part of the damage response to promote cellular plasticity and regeneration. The relative contribution of each cell type and signaling pathway is a critical area of ongoing research, likely dependent on the nature of injury as well as the regional specification within the intestine. Here, we review the current understanding of the multicellular cooperation to restore the intestinal epithelium after damage.

Keywords: Cellular Plasticity; Intestinal Homeostasis; Intestinal Regeneration; Stem Cell Niche.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Diagram of the intestinal structure and the stem cell niche. The intestinal epithelium is a monolayer of cells with a distinct composition along the proximal–distal axis. In both the small intestine and colon, the stem cell compartment is located at the base of the crypt. Stem cells continuously generate transit-amplifying and progenitor populations that further differentiate into 5 main functional cell types: enterocytes, goblet cells, Paneth cells, enteroendocrine cells, and tuft cells. Signaling molecules produced by cells within the epithelial compartment as well as a network of supporting cells establish a gradient to balance between stemness and differentiation in the crypt. WNT, EGF, and Notch signaling are restricted to the base of the crypt and work to maintain intestinal stem cells. BMP antagonists such as Gremlin1/2 also are restricted to the crypt base to establish a BMP signaling gradient from the crypt–villus shoulder to the villus tip and promote differentiation in cells exiting the crypt. BMPRI, bone morphogenetic protein receptor type 1B; BMPRII, bone morphogenetic protein receptor type 2; CSL, CBF-1/Supressor of Hairless/Lag-1; EGFR, epidermal growth factor receptor; PI3K, phosphatidylinositol 3-kinase; RAS, rat sarcoma viral oncogene; RSPO, R-spondin; TCF, transcription factor 4.
Figure 2
Figure 2
Diagram of cells that show cellular plasticity and dedifferentiate after damage. In an injury-dependent manner, there is hierarchical dedifferentiation and mobilization of epithelial cells that contribute to regeneration. Cells from both the secretory and absorptive lineage branches are capable of dedifferentiating to LGR5+ intestinal stem cells to repopulate the crypt after damage.
See this image and copyright information in PMC

References

    1. Barker N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol. 2014;15:19–33. - PubMed
    1. Barker N., van Es J.H., Kuipers J., Kujala P., van den Born M., Cozijnsen M., Haegebarth A., Korving J., Begthel H., Peters P.J., Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–1007. - PubMed
    1. Nicoletti C. Unsolved mysteries of intestinal M cells. Gut. 2000;47:735–739. - PMC - PubMed
    1. Bottcher A., Buttner M., Tritschler S., Sterr M., Aliluev A., Oppenlander L., Burtscher I., Sass S., Irmler M., Beckers J., Ziegenhain C., Enard W., Schamberger A.C., Verhamme F.M., Eickelberg O., Theis F.J., Lickert H. Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates. Nat Cell Biol. 2021;23:23–31. - PubMed
    1. Herring C.A., Banerjee A., McKinley E.T., Simmons A.J., Ping J., Roland J.T., Franklin J.L., Liu Q., Gerdes M.J., Coffey R.J., Lau K.S. Unsupervised trajectory analysis of single-cell RNA-seq and imaging data reveals alternative tuft cell origins in the gut. Cell Syst. 2018;6:37–51 e9. - PMC - PubMed

Publication types