Perelman School of Medicine at the University of Pennsylvania

Song Lab

Neurons in the hippocampus

Neural Stem Cells & Neurogenesis

Mechanisms regulating neural stem cells and neurogenesis

Adult hippocampal neurogenesis reflects a remarkable form of structural plasticity in the mature mammalian brain. Fully characterizing this phenomenon could have far-reaching implications for understanding hippocampal function and revealing fundamental properties of neural development and the regenerative capacity of the mammalian central nervous system. Over the past 15 years, the laboratory has systematically investigated adult hippocampal neurogenesis in mammals at the molecular, cellular, and neuronal circuit levels and reported a number of key findings that have influenced the field. Via genetic clonal analysis, we demonstrated the existence of bona fide neural stem cells in the adult mammalian hippocampus, capable of both self-renewal and multipotent fate specification of progeny. We provided a detailed blueprint about how newborn neuron integration into the existing neuronal circuitry and its underlying molecular, cellular and circuitry mechanisms. In collaboration with Dr. Guo-li Ming, we have discovered critical roles of multiple psychiatric disorder risk genes in regulating the development of newborn neurons during adult hippocampal neurogenesis. We discovered novel mechanisms whereby distinct neuronal circuits influence neural stem cell properties and the development of newborn neurons in the hippocampus. Currently, we are addressing the origin of adult neural stem cells using clonal lineage-tracing approaches and investigating mechanisms regulating adult neural stem cells and neurogenesis using mouse genetic approaches. We have also extended our analyses of neural stem cells and neurogenesis to embryonic cortex and hypothalamus in mice and in humans using brain organoids.


Selected Publications

Persistent Structural Plasticity Optimizes Sensory Information Processing in the Olfactory Bulb

Neuron

Sailor KA, Valley MT, Wiechert MT, Riecke H, Sun GJ, Adams W, Dennis JC, Sharafi S, Ming GL, Song H, Lledo PM. Persistent Structural Plasticity Optimizes Sensory Information Processing in the Olfactory Bulb. Neuron. 2016 Jul 20;91(2):384-96.

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Latent tri-lineage potential of adult neural stem cells in the hippocampus revealed by Nf1 inactivation

Nature Neuroscience

Sun, G.J., Zhou, Y., Ito, S., Bonaguidi, M.A., Stein-O'Brien, G., Kawasaki, N., Modak, N., Zhu, Y., Ming, G-l., and Song, H. (2015). Latent tri-lineage potential of adult neural stem cells in the hippocampus revealed by Nf1 inactivation. Nature Neuroscience 18, 1722-4.

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Neuronal circuitry mechanism regulating adult quiescent neural stem cell fate decision

Nature

Song, J., Zhong, C., Bonaguidi, M.A., Sun, G.J., Hsu1, D., Gu, Y., Meletis, K., Huang, Z.J., Ge, S., Enikolopov, G., Deisseroth, K., Luscher, B., Christian, K., Ming, G-l., and Song, H. (2012). Neuronal circuitry mechanism regulating adult quiescent neural stem cell fate decision. Nature 489, 150-4.

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In vivo clonal analysis reveals self-renew and multipotent adult neural stem cell characteristics

Cell

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-renew and multipotent adult neural stem cell characteristics. Cell 145, 1142-55.

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