Breakthrough as team discover stem cells in the oesophagus.

Despite previous indications to the contrary, the oesophagus does have its own pool of stem cells, said researchers from the University of Pittsburgh in an opensource animal study published in Cell Reports. The findings could lead to new insights into the development and treatment of esophageal cancer and the precancerous condition known as Barrett’s oesophagus.

According to the American Cancer Society, more than 18,000 people will be diagnosed with oesophageal cancer in the U.S. in 2014 and almost 15,500 people will die from it. In Barrett’s oesophagus, the lining of the oesophagus changes for unknown reasons to resemble that of the intestine, though gastro-oesophageal reflux disease or GERD is a risk factor for its development.

The oesophageal lining must renew regularly as cells slough off into the gastrointestinal tract.  To do that, cells in the deeper layers of the oesophagus divide about twice a week to produce daughter cells that become the specialized cells of the lining. Until now, the medical community haven’t been able to determine whether all the cells in the deeper layers are the same or if there is a subpopulation of stem cells there.

The research team grew pieces or organoids of esophageal tissue from mouse samples, and then conducted experiments to identify and track the different cells in the basal layer of the tissue. They found a small population of cells that divide more slowly, are more primitive, can generate specialized or differentiated cells, and have the ability to self-renew, which is a defining trait of stem cells.

It was thought that there were no stem cells in the oesophagus because all the cells were dividing rather than resting or quiescent, which is more typical of stem cells. The findings reveal that there indeed are esophageal stem cells, and rather than being quiescent, they divide slowly compared to the rest of the deeper layer cells.

In future work, the researchers will examine human oesophageal tissues for evidence of stem cell dysfunction in Barrett’s oesophagus disease.

Some scientists have speculated that abnormalities of oesophageal stem cells could be the origin of the tissue changes that occur in Barrett’s disease.  The current and future studies should make it possible to test this long-standing hypothesis.

Source:  University of Pittsburgh Schools of the Health Sciences

 

Because the esophageal epithelium lacks a defined stem cell niche, it is unclear whether all basal epithelial cells in the adult esophagus are functionally equivalent. In this study, we showed that basal cells in the mouse esophagus contained a heterogeneous population of epithelial cells, similar to other rapidly cycling tissues such as the intestine or skin. Using a combination of cell-surface markers, we separated primary esophageal tissue into distinct cell populations that harbored differences in stem cell potential. We also used an in vitro 3D organoid assay to demonstrate that Sox2, Wnt, and bone morphogenetic protein signaling regulate esophageal self-renewal. Finally, we labeled proliferating basal epithelial cells in vivo to show differing cell-cycle profiles and proliferation kinetics. Based on our results, we propose that a nonquiescent stem cell population resides in the basal epithelium of the mouse esophagus.  Cellular Heterogeneity in the Mouse Esophagus Implicates the Presence of a Nonquiescent Epithelial Stem Cell Population.  Lagasse et al 2014.
Because the esophageal epithelium lacks a defined stem cell niche, it is unclear whether all basal epithelial cells in the adult esophagus are functionally equivalent. In this study, we showed that basal cells in the mouse esophagus contained a heterogeneous population of epithelial cells, similar to other rapidly cycling tissues such as the intestine or skin. Using a combination of cell-surface markers, we separated primary esophageal tissue into distinct cell populations that harbored differences in stem cell potential. We also used an in vitro 3D organoid assay to demonstrate that Sox2, Wnt, and bone morphogenetic protein signaling regulate esophageal self-renewal. Finally, we labeled proliferating basal epithelial cells in vivo to show differing cell-cycle profiles and proliferation kinetics. Based on our results, we propose that a nonquiescent stem cell population resides in the basal epithelium of the mouse esophagus. Cellular Heterogeneity in the Mouse Esophagus Implicates the Presence of a Nonquiescent Epithelial Stem Cell Population. Lagasse et al 2014.

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