Hongjun Song PhD
Neurogenesis and Neuro-epigenetics
We are interested in understanding novel mechanisms regulating structural and functional plasticity in the mammalian center nervous system. There are two major topics in the laboratory: one is on mammalian neural stem cells and neurogenesis; and the other is on epigenetic mechanisms in the mammalian nervous system. Our laboratory is using integrated approaches to address the questions, including technologies in molecular biology, cell biology, biochemistry, epigenetics, genomics, bioinformatics, virology, histology, in vivo multiphoton confocal imaging, electrophysiology, mouse genetics and animal behaviors.
(1). Neural stem cells and neurogenesis: Adult neurogenesis occurs in unique microenvironment (niche) and recapitulates the complete neural developmental process in a mature central nervous system, including proliferation and differentiation of neural stem cells, neuronal development and synapse formation, maturation and maintenance. Using retrovirus- and mouse genetics-based strategies, we are interested in identifying both intrinsic and extrinsic mechanisms regulating behaviors of adult neural stem cells and governing synaptic integration of newborn in the adult brain in vivo, using single-cell RNA-seq and clonal lineage-tracing and genetic manipulations. We are addressing the function of adult neurogenesis at multiple levels, including single-cell electrophysiology in acute slices, optogenetics and multi-electrode recordings in vivo, and animal behavior analysis. We have also extended our studies of neural stem cells and neurogenesis to other systems, including embryonic neurogenesis in the hypothalamus.
(2). Neuro-epigenetics: DNA methylation at 5-cytocine has been traditionally considered as very stable epigenetic marks in post-mitotic cells. We recently show that neuronal activity induces active DNA demethylation in post-mitotic neurons in the adult brain in vivo. We further identified an activity-induced active DNA demethylation pathway in neurons, involving conversion of 5-methylcytosine to 5-hydroxylmethylcytosine by TET, followed by base-excision repair. We are interested in identifying molecular machinery mediating active DNA demethylation in neurons and the potential functions of DNA demethylation in neuronal plasticity and mental disorders. We are using combinatory approaches to address these fundamental questions, including biochemistry, protein chip, RNA-seq, Bisulfite-seq, Chip-seq, electrophysiology and animal behavior.