Correlative transmission electron microscopy (TEM) has been performed to complement optical imaging of mouse skin tissue containing a low density of stem cells labeled with the reporter gene beta-gal. These cells produce a clearly visible indigo staining in thick paraffin sections after treatment with the reagent X-gal. After optical microscopy, the paraffin was removed from regions of skin containing one or more labeled cells and the pieces of tissue were re-embedded in plastic. The blocks were then ultramicrotomed to yield serial thin sections that were stained with uranyl acetate and lead citrate, and subsequently imaged at a beam voltage of 120 kV in an energy-filtering transmission electron microscope. By carefully correlating the light and electron micrographs and by examination of the ultrastructure, it was possible to identify the labeled stem cells as keratinocytes.
