Use of isografts to study proliferation and differentiation programs of mouse stomach epithelia

A new model system has been developed for studying the factors that regulate the proliferation and differentiation programs of the principal cell lineages present in the mouse stomach epithelium. When embryonic day 14 (E14) stomachs from C57Bl/6 mice are implanted under the subcutaneous fascia of young adult male CBY/B6 nude mouse recipients, they are rapidly vascularized and begin to grow at rates comparable to the intact stomach of a similarly aged animal. Single- and multilabel immunohistochemical studies, conducted in the intact stomach of E14 to postnatal day 42 (P42) C57Bl/6 mice and in P7, P14, P28, and P42 C57Bl/6 isografts, suggest that the apparently undifferentiated glandular epithelium of E14 stomach already has encoded positional information that permits it to establish regional differences in cell populations even in the absence of exposure to normal luminal contents. Regional differentiation is manifested by the establishment of distinct zones, each composed of gastric units with zone-specific cell lineages. This axial patterning evolves at a rate similar to that of the intact stomach, even though the E14 isograft is placed in the hormonal environment of an adult host and therefore cannot be programmed by normal developmental changes in endocrine status. Moreover, patterning is maintained in isografts despite continuous renewal of its epithelial cell lineages. Although isografts apparently possess autonomously functioning temporal and spatial programs, perturbations were noted in the proliferation and/or differentiation programs of certain lineages, e.g., the rate of accumulation of endocrine cell subpopulations is reduced in these grafts.(ABSTRACT TRUNCATED AT 250 WORDS)