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滕兆乾 研究员

干细胞与脑损伤修复

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- 工作人员:何炫程,工程师;刘聪,特别研究助理
  研究生:王颖颖;李骞;刘潇湉;贺宝东;施若茜;邓钰森;王荐;高兴;王金星
  联合培养研究生:杨瀚晨;李瑞洋

 

  干细胞与脑损伤修复研究组的研究主要聚焦脑创伤、痴呆、精神疾病等重大疾病的病理机制解析与防治手段研发。研究组构建了脑创伤不同时间窗下神经干细胞、小胶质细胞的基因表达谱数据库,筛选出一系列与神经发生异常、细胞凋亡、神经环路异常、突触传递和突触可塑性受损、小胶质细胞表型转化等密切相关的潜在靶标分子;建立了人多能干细胞定向分化小胶质细胞、神经前体细胞、特定功能型神经元、人脑类器官的技术平台。我们尝试综合运用遗传学、分子生物学、生物化学、细胞生物学、生物信息学、行为学、电生理和纳米材料等多学科交叉研究手段,兼顾动物模型和人源化神经模型,从离体和在体两个层面寻找神经相关疾病防治的新靶标,探索神经功能重塑的新方法。

发现精神疾病风险基因MIR137 在神经系统缺失的小鼠呈现出典型的焦虑、认知与社交障碍,鉴定出Pde10a 、Ezh2与KCC2为miR-137调控认知与精神活动的下游靶基因(Nature Neurosci. 2018; Front Mol Neurosci. 2019; Exp Neurobiol. 2020)。

揭示了小胶质细胞 EED 在调控神经元的突触密度(synapse density)以及学习和记忆方面的关键作用及其机理(Mol Psychiatry. 2022)。

研究内容和目标:
围绕脑创伤、神经退行性疾病与精神疾病的生理病理性改变背后的细胞与分子机制、干细胞在神经疾病中的临床应用等科学问题,解析神经病变后大脑内环境变化对神经发生、胶质细胞发生、神经再生的影响及其作用机制,研究小胶质细胞在疾病发生发展过程中表型转化的分子机制,探索通过改善神经再生与可塑性内环境、促进内源神经再生、移植功能型细胞等手段实现神经功能重塑的神经疾病治疗新策略,以期推进神经相关疾病理论的发展与治疗药物的研发。

 

代表性发表论文:

  1. Wang YY, Deng YS, Dai SK, Mi TW, Li RY, Liu PP, Liu C, He BD, He XC, Du HZ, Yang HC, Tang Y, Liu CM*, Teng ZQ*. Loss of microglial EED impairs synapse density, learning, and memory. Molecular Psychiatry  2022, doi: 10.1038/s41380-022-01576-w.
  2. He XC, Wang J, Du HZ, Liu CM*, Teng ZQ*. Intranasal Administration of Agomir-let-7i Improves Cognitive Function in Mice with Traumatic Brain Injury. Cells . 2022, 11(8): 1348.
  3. Liu XT, Liu CM*, Teng ZQ*. Mouse model of voluntary movement deficits induced by needlestick injuries to the primary motor cortex. Journal of Neuroscience Methods  2022, 365: 109380.
  4. Dai SK, Liu PP, Du HZ, Liu X, Xu YJ, Liu C, Wang YY, Teng ZQ*, Liu CM*. Histone crotonylation regulates neural stem cell fate decisions by activating bivalent promoters. EMBO Reports  2021, 22 (10): e52023.
  5. Liu C#, Dai SK#, Shi RX, He XC, Wang YY, He BD, Sun XW, Du HZ, Liu CM*, Teng ZQ*. Transcriptional profiling of microglia in the injured brain reveals distinct molecular features underlying neurodegeneration. Glia  2021, 69 (5): 1292-1306.
  6. Wang ZM, Liu C, Wang YY, Deng YS, He XC, Du HZ, Liu CM*, Teng ZQ*. SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury. Cell Death Discovery  2020, 6 (1): 1-11.
  7. Tang QY, Zhang SF, Dai SK, Liu C, Wang YY, Du HZ, Teng ZQ*, Liu CM*. UTX regulates human neural differentiation and dendritic morphology by resolving bivalent promoters. Stem Cell Reports  2020, 15 (2): 439-453.
  8. Mi TW, Sun XW, Wang ZM, Wang YY, He XC, Liu C, Zhang SF, Du HZ, Liu CM*, Teng ZQ*. Loss of MicroRNA-137 Impairs the Homeostasis of Potassium in Neurons via KCC2. Experimental Neurobiology  2020, 29(2): 138-149.
  9. Liu C#, Dai SK#, Sun Z#, Wang Z, Liu PP, Du HZ, Yu S*, Liu CM*, Teng ZQ*. GA-binding protein GABPβ1 is required for the proliferation of neural stem/progenitor cells. Stem Cell Research  2019, 39: 101501.
  10. Yan HL#, Sun XW#, Wang ZM#, Liu PP#, Mi TW, Liu C, Wang YY, He XC, Du HZ, Liu CM*, Teng ZQ*. MiR-137 Deficiency Causes Anxiety-Like Behaviors in Mice. Frontiers in Molecular Neuroscience  2019, 12: 260.
  11. Cheng Y#, Wang ZM#, Tan W#, Wang X#, Li Y, Bai B, Li Y, Zhang SF, Yan HL, Chen ZL, Liu CM, Mi TW, Xia S, Zhou Z, Liu A, Tang GB, Liu C, Dai ZJ, Wang YY, Wang H, Wang X, Kang Y, Lin L, Chen Z, Xie N, Sun Q, Xie W, Peng J, Chen D*, Teng ZQ*, Jin P*. Partial loss of psychiatric risk gene Mir137 in mice causes repetitive behavior and impairs sociability and learning via increased Pde10a. Nature  Neuroscience  2018, 21(12): 1689-1703.
  12. Duan RS#, Tang GB#, Du HZ#, Hu YW, Liu PP, Xu YJ, Zeng YQ, Zhang SF, Wang RY, Teng ZQ, Liu CM*. Polycomb protein family member CBX7 regulates intrinsic axon growth and regeneration. Cell Death and Differentiation  2018, 25(9): 1598-1611.
  13. Liu PP, Xu YJ, Teng ZQ, Liu CM*. Polycomb Repressive Complex 2: Emerging Roles in the Central Nervous System. Neuroscientist  2018, 24(3): 208-220.
  14. Liu PP, Tang GB, Xu YJ, Zeng YQ, Zhang SF, Du HZ, Teng ZQ*, Liu CM*. MiR-203 Interplays with Polycomb Repressive Complexes to Regulate the Proliferation of Neural Stem/Progenitor Cells. Stem Cell Reports  2017, 9(1): 190-202.
  15. Chen R#, Zhang J#, Fan N#, Teng ZQ#, Wu Y#, Yang H, Tang YP, Sun H, Song Y, Chen C*. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling. Cell  2013, 155(5): 1154-1165.
  16. Liu C#, Teng ZQ#, Santistevan NJ, Szulwach KE, Guo W, Jin P, Zhao X*. Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell  2010, 6(5): 433-44.