Clonal analysis of mouse intestinal epithelial progenitors

Background & Aims: Little is known about the cell lineages leading from stem cells to the various terminally differentiated cell types of the intestinal epithelium. In particular, the existence and characterization of intermediate progenitor types remain open issues, which are discussed in this study. Methods: Chemical mutagenesis was used to genetically mark random intestinal epithelial cells by somatic mutation of the Dlb-1 locus. Intact epithelium was isolated at various times thereafter, and the composition, size, and location of mutant clones were scored. Results & Conclusions: Analysis of clone dynamics showed short-lived (days) progenitors (C-1, M-1, and Mix) yielding one or two cell types and long-lived (months) mucous cell progenitors (M-0), columnar cell progenitors (C-0), and pluripotential stem cells (S) capable of giving rise to all epithelial cell types. Furthermore, study of clonal dispersion, during crypt branching morphogenesis or cell migration, shows that mutant progenitors usually partition into only one of the two daughter crypts and that cells are often widely dispersed in spite of the extensive intercellular junctions in the epithelium.