Expression of Endoderm Stem Cell Markers: Evidence for the Presence of Adult Stem Cells in Human Thyroid Glands

Abstract

Adult stem cells have been detected in several human tissues. The object of this study was to investigate whether they also occur in the human thyroid gland. The expression of the stem cell marker Oct- 4 and the early endodermal markers GATA-4 and HNF4alpha was analyzed in histologic slides and cultured cells derived from goiters, in the FRTL5 cell line, and the HTh74, HTC, C643, and XTC133 thyroid carcinoma cell lines. Stem cell markers were detectable in all primary cultures whereas in the differentiated FRTL5 cell line no expression was observed. Expression of stem cell marker mRNA was not affected by thyrotropin (TSH) stimulation and did not decrease when cells underwent several passages. Immunostaining of cultured cells and of histologic slides of goitrous tissues showed only single cells that were immunoreactive for Oct-4, GATA-4, and HNF4a. Expression of Oct-4 but not of endodermal marker GATA-4 was also detectable in some thyroid carcinoma cell lines. Fluorescence-activated cell sorter (FACS) analysis demonstrated cell populations that were positive for either Oct-4, GATA-4, or HNF4alpha but negative for thyroglobulin. When these putative, FACS-sorted stem cell populations were further analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), expression of all stem cell markers and of Pax8 but not of thyroglobulin mRNA was detectable. These data provide evidence for the presence of adult stem and precursor cells of endodermal origin in the human thyroid gland.