Telomerase is not an epidermal stem cell marker and is downregulated by calcium

The ribonucleoprotein complex telomerase, which was found to be active in g erm line, immortal, and tumor cells, and in cells from continuously renewin g normal tissues such as epidermis or bone marrow, is thought to be correla ted with an indefinite life span. Therefore, it has been postulated that in the normal tissues, telomerase activity may be restricted to stem cells, t he possible precursors of tumor cells. Here, we demonstrate that a 56% enri ched population of epidermal stem cells exhibited less telomerase activity than the more actively proliferating transit amplifying cells, which are de stined to differentiate after a finite number of cell divisions. Thus telom erase is not a stem cell marker. In human epidermis we found a heterogeneou s expression of the telomerase RNA component (hTR) within the basal layer, with clusters of hTR-positive cells showing variable activities. Histone-3 expressing S-phase basal cells were distributed evenly, illustrating that h TR upregulation may not strictly be correlated with proliferation. We furth er show for human epidermal cells that differentiation-dependent downregula tion of telomerase correlates with Ca++-induced cell differentiation and th at increasing the amount of Ca++ but not Mg++ or Zn++ reduced telomerase ac tivity in a dose-dependent manner in a cell-free system (differentiation-in dependent), Furthermore, addition of ethyleneglycol-bis(beta-aminoethyl eth er)-N,N,N',N'-tetraacetic acid completely reversed this Ca++-induced inhibi tion. These data indicate that Ca++ is not only an important regulator of e pidermal differentiation but also a key regulator of telomerase.