Macroscopic intestinal colonies of mice as a tool for studying differentiation of multipotential intestinal stem cells.

Macroscopic nodules composed of regenerating intestinal epithelium were developed within an area of the murine jejunum ulcerated by X-irradiation (1700 rads). The authors investigated whether such intestinal nodules were clonal and whether this method was useful as a tool for studying differentiation of intestinal stem cells. For examination of the clonality, intestinal nodules were produced in the jejunum of (C57BL/6 X DS)F1-Pgk-1b/Pgk-1a mice that carried X-chromosome inactivation mosaicism for the phosphoglycerate kinase gene. All intestinal nodules contained only 1 type of phosphoglycerate kinase, suggesting the monoclonal origin of nodules. Histochemical and electron microscopic studies showed the presence of absorptive epithelial, goblet, and entero-endocrine cells in most intestinal nodules, suggesting the multipotentiality of the nodule-forming stem cells. Moreover, villi developed on the top of some intestinal nodules, implicating the potential of the multipotential stem cell to construct the highly organized structure. The result indicates that the intestinal nodule method is useful for investigating differentiation potentials of multipotential intestinal stem cells.