Identification of Candidate Murine Esophageal Stem Cells Using a Combination of Cell Kinetic Studies and Cell Surface Markers

Abstract

The identification and characterization of esophageal stem cells are critical to our understanding of the biology of the esophageal epithelium in health and disease. However, the proliferative compartment within the mouse esophageal epithelium remains poorly characterized. Here, we report that the basal cells of the mouse esophagus can be separated into three phenotypically and functionally distinct subpopulations based on the expression of ␣ 6 integrin and transferrin receptor (CD71). Cells that express high levels of ␣ 6 integrin and low levels of CD71, termed ␣ 6 bri CD71 dim , are a minor subpopulation of small and undifferentiated cells that are enriched for label-retaining cells and thus represent a putative esophageal stem cell population. Conversely, cells expressing high levels of both ␣ 6 integrin and CD71 (␣ 6 bri CD71 bri ), the majority of basal esophageal cells, are enriched for actively cycling cells and therefore represent a transit-amplifying population. Kinetic analyses revealed that a third cell population, which is ␣ 6 integrin-dim and CD71-bright (␣ 6 dim ), is destined to leave the basal layer and differentiate. STEM CELLS 2007;25:313-318

Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration

“…In the lineage tracing experiment, GFP-labeled cells were detected at multiple time points (from D1 to D56 following recombination) in the esophagus ( Figure 1E) as well as in the forestomach (Supplemental Figure 2C) and the esophageal epithelium. Although their existence has been suggested through label-retaining studies and 3D organoid culture assays, their true identity remains to be fully described (9)(10)(11)(12)(13)(14). We reported previously that a side population of mouse esophageal basal cells is capable of DNA label retention and also excludes Hoechst dye, a feature associated with the presence of ATP-binding cassette membrane transporters that has been linked to stem cell activity in several tissues (e.g., hematopoietic stem cells) (15).…”

“…Using a more targeted approach, we also determined the expression of several membrane proteins that have been associated previously with esophageal epithelial stemness potential (9,11,12,31). Table 2).…”

Cell competition: Winning out by losing notch

“…31,32 It is not perhaps surprising that cells differ in their ability to survive isolation by prolonged typsinization and then proliferate in a non-physiological, often growth factor loaded, culture environment. 32 Marker expression may depend on factors such as whether cells are in a particular phase of the cell cycle or initiating differentiation, that may impact on colony forming efficiency.…”

Biomarkers, Stem Cells and Esophageal Cancer

“…Esophageal SP cells have the ability to home in on and differentiate to esophagus cells as shown by in vitro and in vivo esophageal injury models. A rare stem cell population expressing high levels of 6 -integrin and low levels of CD71 was characterized in the basal layer of the mouse esophagus and whose final function is to form and/or regenerate the suprabasal layers (Croagh et al, 2007). A population of stem cells characterized by low expression of 1-integrin and high expression of 2-laminin chain was isolated from the human esophagus with the ability to reconstitute the esophageal epithelium in vitro (Seery and Watt, 2000).…”