|Department Affiliations||Institute for Cell Engineering Department of Neurology Department of Neuroscience|
|Rank||Professor, Director, Stem Cell Program|
|SOM Address||759 Miller Research Building|
There are two major topics in the laboratory: one is on adult mammalian neural stem cells and neurogenesis; and the other is on epigenetic DNA modifications in the mature nervous system. We are also interested in brain disorders associated with these two topics, including autism, Rett syndrome, schizophrenia, depression, degenerative neurological disorders and brain tumors. Our laboratory is using integrated approaches, 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). Adult 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 progenitor/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. In addition, 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.
2). Epigenetic DNA modifications in neurons: 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 DNA 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, single-cell RNA-seq, Bisulfite-seq, Chip-seq, electrophysiology and animal behavior.
- Shin, J., Berg, D.A., Zhu, Y., Shin, J.Y., Song, J., Bonaguidi, M.A., Enikolopov, G., Nauen, D.W., Christian, K.M., Ming, G.L., and Song H. (2015). Single-Cell RNA-Seq with Waterfall reveals molecular cascades underlying adult neurogenesis. Cell Stem Cell [Epub ahead of print].
- Yu, H., Su, Y., Shin, J., Zhong, C., Guo, J.U., Weng, Y.L., Gao, F., Geschwind, D.H., Coppola, G., Ming, G.L., and Song, H. (2015). Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair. Nat Neurosci. 18:836-43.
- Wen, W., Nguyen, H.N.N., Guo, Z., Lalli, M.A., Wang, X., Su, Y., Kim, N-S., Yoon, K.J., Shin, J., Zhang, C., Makri, G., Nauen, D., Yu, H., Guzman, E., Chiang, C-H., Yoritomo, N., Kaibuchi, K., Zou, J., Christian, K.M., Cheng, L., Ross, C.A., Margolis, R.L., Chen, G., Kosik, K.S., Song, H., and Ming, G-l. (2014). Synaptic dysregulation in a human iPS cell model of mental disorders. Nature 515:414-8.
- Christian, K.M., Song, H., and Ming, G.L. (2014). Functions and dysfunctions of adult hippocampal neurogenesis. Annu Rev Neurosci. 37:243-62.
- Guo JU, Su Y, Shin JH, Shin J, Li H, Xie B, Zhong C, Hu S, Le T, Fan G, Zhu H, Chang Q, Gao Y, Ming GL, Song H. (2014). Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci. 17:215-22.
- Jang MH, Bonaguidi MA, Kitabatake Y, Sun J, Song J, Kang E, Jun H, Zhong C, Su Y, Guo JU, Wang MX, Sailor KA, Kim JY, Gao Y, Christian KM, Ming GL, Song H. (2013). Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. Cell Stem Cell 12:215-23.
- Song, J., Zhong, C., Bonaguidi, M.A., Sun, G.J., Hsu, D., Gu, Y., Meletis, K., Huang, Z.J., Ge, S., Enikolopov, G., Deisseroth, K., Luscher, B., Christian, K.M., Ming, G.L., and Song, H. (2012). Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature 489:150-4.
- Guo, J. U., Ma, D.K., Mo, H., Ball, M.P., Jang, M.H., Bonaguidi, M.A., Balazer, J.A. Eaves, H.L., Xie, B., Ford, E. Zhang, K., Ming, G-l., Gao, Y., and Song, H. (2011). Neuronal activity modifies DNA methylation landscape in the adult brain. Nat. Neurosci. 14:1345-51.
- Bonaguidi, M.A., Wheeler, M.A., Shapiro, J.S., Stadel, R.P., Sun, G.J., Ming, G-l., and Song, H. (2011). In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell 145, 1142-55.
- Guo, J.U., Su, Y., Zhong, C., Ming, G.L., and Song, H. (2011). Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145:423-34.
- Ma, D.K., Jang, M.H., Guo, J.U., Kitabatake, Y., Chang, M.L., Pow-Anpongkul, N., Flavell, R.A., Lu, B., Ming, G.L., Song, H. (2009). Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074-7.
- Duan, X., Chang, J.H., Ge, S., Faulkner, R.L., Kim, J.Y., Kitabatake, Y., Liu, X.B., Yang, C.H., Jordan, J.D., Ma, D.K., Liu, C.Y., Ganesan, S., Cheng, H.J., Ming, G.L., Lu, B., Song, H. (2007). Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 13:1146-58.
- Ge, S., Goh, E.L., Sailor, K.A., Kitabatake, Y., Ming, G.L., Song, H. (2006). GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439:589-93.