Ten-Eleven Translocation 1 and 2 Confer Overlapping Transcriptional Programs for the Proliferation of Cultured Adult Neural Stem Cells.

Abstract

Adult neurogenesis originates from neural stem cells (NSCs) in specific regions of the adult brain. The molecular mechanisms that control the self-renewal and multipotency of NSCs have not been fully elucidated. In recent years, emerging evidence has revealed that ten-eleven translocation (TET) family DNA dioxygenases TET1 and TET2 play important roles in the central nervous system. Here, I present evidence that Tet1 and Tet2 are expressed in cultured NSCs derived from adult mouse brain and play an important role in the proliferative self-renewal of NSCs in an undifferentiated state. The investigation of intracellular molecular networks involving both Tet1 and Tet2 by gene knockdown and comprehensive genetic analyses showed that overlapping molecular mechanisms involving TET1 and TET2 regulate the expression of at least 16 genes required for DNA replication and cell cycle control. Interestingly, transcriptional regulation of the selected gene through TET1 and TET2 did not correlate with direct CpG demethylation of the gene promoter. These findings suggest that TET1 and TET2 play an important role in the proliferation of NSCs in the adult mouse brain by specifically regulating common genes for DNA replication and the cell cycle.