Various facets of the intercellular heterogeneity in thyroid primary culture.

The mechanisms that generate the intercellular heterogeneity of functional and proliferation responses in a tissue are generally unknown. In thyroid gland, this heterogeneity is peculiarly marked and it was suggested that it could result from the coexistence of (epi)genetically different subpopulations of thyrocytes. As summarized in this short review, qualitative or quantitative intercellular heterogeneities have been found at each levels of our "in situ" investigations of morphological, differentiation and proliferative responses of unselected dog thyrocytes in primary culture. These different heterogeneities are unrelated at the individual cell level, which does not indicate the coexistence in thyroid of cell subpopulations stably expressing special properties. Nevertheless, using a double labeling methodology that allows to trace the proliferative behavior of some cells, we show how cell division may stably affect further proliferation responses and how a local synchrony of the dividing cells can result in a stable heterogeneity with a regional, patchy pattern, which resembles the one characterizing multinodular goiter.