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Am J Physiol Gastrointest Liver Physiol. 2015 Dec 15;309(12):G975-87. doi: 10.1152/ajpgi.00244.2015. Epub 2015 Oct 22.

Nkx2.2 is expressed in a subset of enteroendocrine cells with expanded lineage potential.

Author information

1
Department of Genetics and Development, Columbia University Medical Center, New York, New York;
2
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee;
3
Department of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York; and.
4
Department of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York; and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.
5
Department of Genetics and Development, Columbia University Medical Center, New York, New York; lgs2@columbia.edu.

Abstract

There are two major stem cell populations in the intestinal crypt region that express either Bmi1 or Lgr5; however, it has been shown that other populations in the crypt can regain stemness. In this study, we demonstrate that the transcription factor NK2 homeobox 2 (Nkx2.2) is expressed in enteroendocrine cells located in the villus and crypt of the intestinal epithelium and is coexpressed with the stem cell markers Bmi1 and Lgr5 in a subset of crypt cells. To determine whether Nkx2.2-expressing enteroendocrine cells display cellular plasticity and stem cell potential, we performed genetic lineage tracing of the Nkx2.2-expressing population using Nkx2.2(Cre/+);R26RTomato mice. These studies demonstrated that Nkx2.2+ cells are able to give rise to all intestinal epithelial cell types in basal conditions. The proliferative capacity of Nkx2.2-expressing cells was also demonstrated in vitro using crypt organoid cultures. Injuring the intestine with irradiation, systemic inflammation, and colitis did not enhance the lineage potential of Nkx2.2-expressing cells. These findings demonstrate that a rare mature enteroendocrine cell subpopulation that is demarcated by Nkx2.2 expression display stem cell properties during normal intestinal epithelial homeostasis, but is not easily activated upon injury.

KEYWORDS:

Bmi1; Lgr5; Nkx2.2; enteroendocrine cells; stem cells

PMID:
26492922
PMCID:
PMC4683302
DOI:
10.1152/ajpgi.00244.2015
[Indexed for MEDLINE]
Free PMC Article

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