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

Gross S, Balderes D, Liu J, Asfaha S, Gu G, Wang TC, Sussel L
Am J Physiol Gastrointest Liver Physiol. 2015 309 (12): G975-87

PMID: 26492922 · PMCID: PMC4683302 · DOI:10.1152/ajpgi.00244.2015

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.

Copyright © 2015 the American Physiological Society.

MeSH Terms (23)

Animals Basic Helix-Loop-Helix Transcription Factors Biomarkers Cell Differentiation Cell Lineage Cell Proliferation Cells, Cultured Enteroendocrine Cells Genotype Homeodomain Proteins Intestinal Mucosa Luminescent Proteins Mice, Inbred C57BL Mice, Transgenic Nerve Tissue Proteins Phenotype Pluripotent Stem Cells Polycomb Repressive Complex 1 Proto-Oncogene Proteins Receptors, G-Protein-Coupled Transcription Factors Whole-Body Irradiation Zebrafish Proteins

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