Parthenogenetic stem cells in postnatal mouse chimeras

The ability of parthenogenetic (pg) cells to contribute to proliferating stem cell populations of postnatal aggre gation chimeras was investigated. Using DNA in situ analysis, pg participation was observed in highly regen erative epithelia of various regions of the gastrointesti nal tract, e.g., stomach, duodenum and colon, in the epithelia of tongue and uterus and in the epidermis. Pg cells also contributed to the epithelium of the urinary bladder, which is characterized by a relatively slow cel lular turnover. Using a sensitive proliferation marker to determine division rate of pg and normal (wt) cells in tissues of a 24-day-old chimera, no significant differences between pg and fertilized cells were observed. However, in colon and uterus of a pg wt chimera aged 101 days, a significant loss of proliferative capacity of pg cells was found. In the colon, this loss of proliferative potential was accompanied by an altered morphology of pg crypts. In general, they were situated at the periphery of the epithelium and lacked access to the lumen, with consequent cystic enlargement and flattened epithelium. No obvious morphological changes were observed in the pg-derived areas of the uterine epithelium of this chimera. Our results provide evidence that pg cells can persist as proliferating stem cells in various tissues of early postnatal chimeras. They suggest that pg-derived stem cells may cease to proliferate in restricted areas of the gastrointestinal tract and in the uterine epithelium of pg wt chimeras of advanced age. However, no indica tions of such a loss of proliferative potential of pg cells could be observed in other areas of the digestive tract, e.g., in the stomach and duodenum, or in oral epithe lium and in the epidermis. These findings argue for a high degree of specificity of selection against pg cells in postnatal life. They also suggest that an impaired proliferative capacity is not a general feature of pg cells. Hence, it is possible that, to explain the impaired growth of of pg wt chimeras and the overall stringent selection against pg cells in such chimeras during fetal development, additional and/or alternative causes apart from a decreased proliferative potential of pg cells have to be considered. Apart from their contribution to the endodermderived epithelia of stomach, gut and uterus, to the mesoderm-derived epithelium of uterus and to ecto derm-derived oral epithelium and epidermis, pg-derived cells differentiated into the mesoderm-derived mesenchymal cells of the stromal layers that lie between the epithelial cells and smooth muscle of stomach, gut, uterus and urinary bladder. Contribution to smooth muscle was also observed. Thus our results show that pg cells are able to dif ferentiate into various cell types of different embryonic origin in tissues of composite structure. Summary