A complete understanding of the structure and function of neural systems will require integrating information from multiple levels of analyses. Analyzing the behavior of single cells in vivo has been one of the most daunting challenges but is necessary to appreciate the extent of functional heterogeneity within single structures or cell populations. Many neural processes can be described at the population level, but there are several domains where it is critical to identify molecular and functional properties at the single cell level. Our laboratory developed a "single-cell genetic" approach to manipulate target genes in newborn neurons using retroviruses that led to a number of critical discoveries. Our identification of bona fide neural stem cells in the adult brain required clonal analysis to demonstrate that individual precursor cells are capable of both self-renewal and giving rise to multiple cell types, thus settling a debate in the field over whether neurons and glia were generated from lineage-restricted progenitors or true stem cells. We have recently developed single-cell RNA-seq technology and a bioinformatics pipeline named “Waterfall” to investigate molecular cascades during a continuous biological process. Currently, we are expanding our single-cell analysis to ATAC-seq, HiC, ChIP-seq, proteomes, and molecular interactomes.
Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis
Shin J, Berg DA, Zhu Y, Shin JY, Song J, Bonaguidi MA, Enikolopov G, Nauen DW, Christian KM, Ming GL, Song H. Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis. Cell Stem Cell. 2015 Sep 3;17(3):360-72. doi: 10.1016/j.stem.2015.07.013. Epub 2015 Aug 20.
Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis
Jang, M., Bonaguidi, M.A., Kitabatake, Y., Sun, J., Song, J., Kang, E., Jun, H., Zhong, C., Su, Y., Guo, J.U., Wang, M.X., Sailor, K.A., Kim, J.Y., Gao, Y., Christian, K.M., Ming, G-l., and Song, H. (2013). Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. Cell Stem Cell 12, 215-23.
In vivo clonal analysis reveals self-renew and multipotent adult neural stem cell characteristics
Bonaguidi, M.A., Wheeler, M., Shapiro, J.S., Stadel, R., 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.
GABA regulates synaptic integration of newly generated neurons in the adult brain
Ge, S-y., Goh. E.L.K., Sailor, K.A., Kitabatake, Y., Ming, G-l*. and Song, H-j*. (2006). GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439, 589-593.