It is now recognized that cell identity is more fluid, and tissues more plastic, than previously thought. The plasticity of cells is relevant to diverse fields, most notably developmental and stem cell biology, regenerative medicine, and cancer biology. To date, a comprehensive and uniform nomenclature to define distinct cell states and their injury-induced interconversions has been elusive. The first Keystone Symposium devoted exclusively to cellular plasticity in regeneration and tumorigenesis was held on January 2019 in Keystone, Colorado, and featured a workshop on terminology in the cell plasticity field. Definitions for terms such as plasticity, de- and transdifferentiation, reversion, and paligenosis were discussed. Here, we summarize the content and tenor of the symposium and nomenclature-focused workshop with regard to terms in the field. We outline the challenges with current definitions and recommend best practices and approaches to developing an accurate and acceptable nomenclature in the future.

Background and aims

Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.

Methods

Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.

Results

FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, generated insulin- and C-peptide-immunoreactive cells, and raised Neurog3 messenger RNA. Gene expression and ChIP- seq experiments identified the cell cycle regulator cyclin E1 (CCNE1) as a FOXO1 target.

Conclusion

FOXO1 is expressed in a subset of stomach cells. Its ablation increases parietal cells and yields insulin-immunoreactive cells, consistent with a role in lineage determination.