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滕兆乾 研究员

干细胞与脑损伤修复

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- 成员:滕兆乾,何炫程,王志萌,刘聪,王颖颖,孙晓雯,李骞,刘潇湉,刘潇,贺宝东,施若茜,邓钰森

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  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诊疗手段研发。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培养小胶质细胞、神经前体细胞、兴奋性神经元、抑制性神经元、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、行为学和电生理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Pde10aEzh2为miR-137调控认知与精神活动的下游靶基因(Nature Neuroscience 2018; Frontiers in Molecular Neuroscience 2019)。

首次报道GABP在神经干细胞增殖与分化中行使不可或缺的调控功能,提出了“GABPβ1S代偿GABPβ1L调节神经发育”的新假说(Stem Cell Research 2019)。

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、促进内源性神经发生、移植干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. 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 Aug;39:101501.
  2. 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 Oct 30;12:260.
  3. Xu YJ, Liu PP, Ng SC, Teng ZQ, Liu CM*. Regulatory Networks between Polycomb Complexes and Non-coding RNAs in Central Nervous System. Journal of Molecular Cell Biology. 2019 Jul 10. pii: mjz058.
  4. Zhu W, Zhang B, Li M, Mo F, Mi T, Wu Y, Teng ZQ, Zhou Q*, Li W*, Hu B*. Precisely controlling endogenous protein dosage in hPSCs and derivatives to model FOXG1 syndrome. Nature Communications. 2019 Feb 25;10(1):928.
  5. Liu PP, Xu YJ, Dai SK, Du HZ, Wang YY, Li XG, Teng ZQ, Liu CM*. Polycomb Protein EED Regulates Neuronal Differentiation through Targeting SOX11 in Hippocampal Dentate Gyrus. Stem Cell Reports. 2019 Jul 9;13(1):115-131.
  6. 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 Dec;21(12):1689-1703.
  7. Sun XW, Liu CM, Teng ZQ*. Commentary: Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Frontiers in Molecular Neuroscience. 2018 Sep 20;11:340.
  8. 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 Sep;25(9):1598-1611.
  9. Wu M, Zhang D, Bi C, Mi T, Zhu W, Xia L, Teng ZQ, Hu B*, Wu Y*. A Chemical Recipe for Generation of Clinical-Grade Striatal Neurons from hESCs. Stem Cell Reports. 2018 Sep 11;11(3):635-650.
  10. Liu PP, Xu YJ, Teng ZQ, Liu CM*. Polycomb Repressive Complex 2: Emerging Roles in the Central Nervous System. Neuroscientist. 2018 Jun; 24(3): 208-220.
  11. Tang GB#, Zeng YQ#, Liu PP#, Mi TW, Zhang SF, Dai SK, Tang QY, Yang L, Xu YJ, Yan HL, Du HZ, Teng ZQ*, Zhou FQ*, Liu CM*. The Histone H3K27 Demethylase UTX Regulates Synaptic Plasticity and Cognitive Behaviors in Mice. Frontiers in Molecular Neuroscience. 2017 Aug 24;10:267.
  12. 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 Jul 11;9(1):190-202.
  13. 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 Nov 21;155(5):1154-1165.
  14. 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 May 7;6(5):433-44.