Turnover of NESTIN-Negative Neural Progenitors Into NESTIN-Positive State by the Lack of JMJD3

Epigenetic regulation has fundamental roles in the maintenance and differentiation of neural stem cells as well as fate determination of neural lineage. Although neural differentiation is irreversible under physiological conditions, neural dedifferentiation into NSCs was observed under a damaged condition and in an aged brain. However, molecular mechanisms triggering neural fate regulation still remain to be elucidated. In this study, we show that a neural turnover in the adult brain is induced by the lack of JMJD3 using NSC-visualized neural JMJD3 deleted mice. In the JMJD3 deleted brain, a marked expansion of the Nestin-GFP positive population in the hippocampus was observed. Moreover, neurosphere assays revealed not only that JMJD3 deleted neurospheres showed a significantly higher self-renewal potential but also that Nestin-negative neural progenitors converted into a Nestin-positive state in the absence of JMJD3. Intriguingly, a combination of upregulation of Plagl2 and inhibition of Dylk1a as well as increased expressions of HMGAs were detected in the neurospheres lacking JMJD3, suggesting that the lack of JMJD3 could enhance rejuvenation of chromatin state. These results suggest that JMJD3 could be involved in the fate regulation of NSC/NPCs and could provide novel and important insights to promote neural repair and regeneration.