Fox Transcription Factors Regulate The Gene Expression Of Stem Cells

The important properties of stem cells, such as maintenance of quiescence, self-renewal capacity, and differentiation potential, have propelled this exciting field and presently form a common theme of research in developmental biology and medicine.It is involved in complex networks of transcription factors, different signaling molecules and the interaction of genetic and epigenetic events.Fox transcription factors are intimately involved in the regulation of organism development, cell differentiation and proliferation. This paper emphasis on studying the Fox transcription factor FoxM1 and FoxA1 regulate the gene expression of stem cells. We take P19EC as a model for stem cell reasearch and use the three kinds of reasearch systems: P19EC retinoic acid(RA) induced neural differentiation, knockdown Fox transcription factors and overexpression of Fox transcription factors by adenovirus.FoxM1 is broadly expressed in actively dividing cells and is crucial for cell cycle-dependent gene expression in the G2 phase of the cell cycle. It is expressed in all embryonic tissues, adult tissues with a high proliferation index and cancer-derived cell lines. It is expressed in stem cells, while its expression is decrease when cells differentiation.With RA-induced neural differentiation, alkaline phosphatase activity declined, pluripotency gene can be reduced. Inhibit FoxM1 expression, the intracellular alkaline phosphatase activity decreased and pluripotency related genes also decreased.The results suggest FoxM1 mediate the self-renewal and pluripotency of stem cell.Transcription factor FoxA1 play important roles in cellular proliferation and differentiation during embryonic development and also play emerging roles in cancer.FoxA1 plays a role in the early development of central nervous system and endoderm-derived organs like liver and pancreas. FoxA1 induced at early time points during RA-induced accompanied by expression of Nanog decline,the neural developmental gene expression in succession. Overexpression of FoxA1 alone in P19 cells decrease the level of Nanog and Nestin increased. Knockout FoxA1 lead to expression of Shh and Nestin blocked. This paper find that increased transcription factor FoxA1 can stimulate neural differentiation.