Evidence of adult stem cells in the human thyroid: Expression of endoderm stem cell markers GATA-4, HNF-4α and AFP in human thyroid cells derived from nodular and non-nodular thyroid tissue

Abstract

Adult stem cells have been identified in several human tissues such as the bone marrow, the liver, the dermis and the gut. GATA-4 and HNF-4α are transcription factors used to characterize stem cells of endodermal origin. GATA-4 has been found in several multipotent, undifferentiated endocrine tissues, such as the granulosa cells of intermediary and small primary ovarian follicles, the fetal adrenal cortex and the developing testis. HNF-4α has been used as a marker for primary endoderm and has been found in the liver, the kidneys, the pancreas and the gonads. AFP is an endoderm marker of unknown biological role, which characterizes undifferentiated cells of endodermal origin such as liver stem cells. We report that thyroid cells obtained from nodular and non-nodular thyroid tissues express GATA-4, HNF-4α and AFP in vitro, on the mRNA and protein level. We further analyzed the expression of these factors after several cell passages. We observed that while GATA-4 and HNF-4α continue to be expressed after many passages, AFP signal was no longer detectable after the first subculture. According to the concept of the Suppression of Asymmetric Cell Kinetics (SACK) theory, we propagated cells with Xanthosine, a nucleoside-analogue. To clarify the mechanisms of intracellular regulation of these factors we conducted stimulation experiments with forskolin, a cAMP analogue. We found no significant change in GATA-4 or HNF-4α expression after forskolin stimulation. Finally, we observed no expression of GATA-4, HNF-4α or AFP in three known thyroid carcinoma lines. We conclude that the selective expression of these stem cell markers in non-malignant thyroid tissue according to the principles of Asymmetric Cell Kinetics might imply the existence of adult stem cells in the human thyroid gland.