Lin28: Regulation of adult neurogenesis during aging

报告题目：Lin28: Regulation of adult neurogenesis during aging

报告人：谷岩  研究员

时    间：2020年10月23日 9:30-10:30

地    点：徐州医科大学主校区科教楼D403

主    持：肖诚

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谷岩，浙江大学医学院研究员，博士生导师。毕业于中国科学技术大学，先后在美国俄勒冈健康科学大学和纽约州立大学石溪分校任博士后和研究学者，自2015年9月至今，任浙江大学基础医学院研究员。入选中组部“青年千人”计划和浙江大学“百人计划”。多年从事成体神经发生与学习记忆的基础研究。系统地研究了成体海马神经发生的调控、新生神经元在学习记忆中的生理功能，以及记忆的编码与遗忘的细胞机制。以第一作者或通讯作者在Science和Nature Neuroscience等期刊发表了很有影响力的研究论文。今年1月，以第一通讯作者发表在Science上题为“Microglia mediate forgetting via complement-dependent synaptic elimination”是2020年最受读者关注的20篇由中国团队参与完成的Science原创研究论文之一。

代表性论文：

1. Wang C#, Yue H#, Hu Z, Shen Y, Ma J, Li J, Wang XD, Wang L, Sun B, Shi P, Wang L*, Gu Y*. Microglia mediate forgetting via complement-dependent synaptic elimination. Science. 2020 Feb 7;367(6478):688-694.

2. Gu Y, Arruda-Carvalho M, Wang J, Janoschka SR, Josselyn SA, Frankland PW, Ge S* Optical controlling reveals time-dependent roles for adult-born dentate granule cells. Nature Neuroscience 2012, Dec; 15(12), 1700-1706.

3. Kumamoto N#, Gu Y#, Wang J, Janoshka S, Takemaru K-I, Levine J, Ge S* A role for primary cilia in glutamatergic synaptic integration of adult-born neurons. Nature Neuroscience 2012, Feb; 15(3), 399-405, S1. (# Equal contribution)

报告摘要  Wnt ligands and antagonists within the hippocampal neurogenic niche regulate the proliferation of neural progenitor cells and the development of new neurons, and mediate age-associated decline of neurogenesis and cognitive functions. We find that Lin28a remains existent in neural progenitor cells and granule neurons in the adult hippocampus and decreases with aging. Conditional knocking out Lin28a from the hippocampal neural progenitor cells impairs neurogenesis and the responsiveness of neural progenitor cells to niche Wnt signals. Whereas, overexpression of Lin28a increases proliferation of neural progenitor cells, and promotes the functional integration of newborn neurons. Moreover, overexpression of Lin28a in hippocampal neural progenitor cells increases neurogenesis, resulting in improved pattern separation, and restores the decreased pattern separation in aging mice. These data suggest that Lin28a regulates adult hippocampal neurogenesis as an intracellular mechanism by responding to niche Wnt signals, and is involved in age-associated decline of hippocampal neurogenesis and related cognitive functions.