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焦建伟　研究员

神经干细胞增殖与分化

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- 工作人员：季芬，李红
- 博士后：苏立波
- 研究生：李妍昕，张东明，李忠秋，李晨晓，王稳稳，冯超，邹文政，赵津悦，王元元，马红燕，张梦甜，谢彦贞，吕妤卿，王岩岩

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　　实验室主要从事脑发育及疾病机理研究，神经干细胞增殖与分化调控研究，遗传和表观遗传对神经发育调控机制研究，以及神经细胞转分化研究。目前承担国家基金委杰出青年基金，重点项目，科技部重点研发项目，中科院先导项目等。

　　1. 研究表观遗传分子调控调控神经干细胞的增殖和神经元产生机制。已有的研究表明某些表观遗传分子参与调控神经干细胞的产生、增殖、分化，但对哪些表观遗传分子如何参与这一过程并不清楚。我们主要研究一个表观遗传分子-组蛋白甲基转移酶Dot1L（H3K79 Methyltransferase）如何调控神经干细胞的增殖和分化。另外，对另外一个表观遗传分子-组蛋白甲基转移酶Ezh2 （H3K27 methyltransferase）进行研究。体外通过增殖以及分化实验进行表观遗传分子调控神经干细胞的机制研究，同时借助基因敲除或条件性基因敲除小鼠进行体内研究。

　　2. 研究miRNAs对神经干细胞增殖分化的影响。对不同的神经细胞进行miRNAs芯片分析，筛选差异表达的miRNAs。然后通过过表达或抑制实验，以及靶蛋白预测实验，研究miRNAs是如何参与调控神经干细胞的发育分化。

　　3. 正在研究从非神经细胞到神经元的转分化。我们正在尝试不同转录因子的组合是否将成纤维细胞转分化为神经元；另外正在探索非整合病毒体系是否将非神经细胞转分化为神经元。



研究纤维细胞到神经元的转分化



研究神经干细胞自我更新和命运决定的表观遗传调控机制

 

研究内容和目标:
神经干细胞(neural stem cell，NSC)是一类具有分裂潜能和自我更新能力的干细胞，对神经干细胞的研究，不仅让我们对神经干细胞的生成及神经系统的发育有进一步的了解，同时，对许多疾病、老化甚至肿瘤的治疗上均具有许多重要的影响。阐明神经干细胞增生，发育的相关机理，可以为预防和治疗脑部肿瘤，以及神经损伤后的干细胞治疗提供了重要理论基础。
实验室主要从事神经干细胞的增殖和分化研究，以及非神经细胞到神经细胞的重编程和转分化研究。

 

代表性发表论文:

  1. Ji F, Wang W, Feng C, Gao F, Jiao J*. Brain-specific Wt1 deletion leads to depressive-like behaviors in mice via the recruitment of Tet2 to modulate Epo expression. Mol Psychiatry. 2020 doi: 10.1038/s41380-020-0759-8.
  2. Feng C, Zhao J, Ji F, Su L, Chen Y, Jiao J*. TCF20 dysfunction leads to cortical neurogenesis defects and autistic-like behaviors in mice. EMBO Rep. 2020 doi:10.15252/embr.201949239.
  3. Liang Q, Su L, Zhang D, Jiao J*. CD93 negatively regulates astrogenesis in response to MMRN2 through the transcriptional repressor ZFP503 in the developing brain. Proc Natl Acad Sci USA. 2020 117:9413-9422.
  4. Su L, Lei X, Ma H, Feng C, Jiang J, Jiao J*. PRDM16 orchestrates angiogenesis via neural differentiation in the developing brain. Cell Death Differ. 2020 doi: 10.1038/s41418-020-0504-5.
  5. Li Y, Jiao J*. Deficiency of TRPM2 leads to embryonic neurogenesis defects in hyperthermia. Science Advances. 2020 6:eaay6350.
  6. Li Z, Li Y, Jiao J*. Neural progenitor cells mediated by H2A.Z.2 regulate microglial development via Cxcl14 in the embryonic brain. Proc Natl Acad Sci USA. 2019 116:24122-24132.
  7. Xia W, Su L, Jiao J*. Cold-induced protein RBM3 orchestrates neurogenesis via modulating Yap mRNA stability during cold stress. J Cell Biol. 2018 217:3464-3479.
  8. Su L, Xia W, Shen T, Liang Q, Wang W, Li H, Jiao J*. H2A.Z.1 crosstalk with H3K56-acetylation controls gliogenesis through the transcription of folate receptor. Nucleic Acids Res. 2018 46:8817-8831.
  9. Lei X, Jiao J*. UTX affects neural stem cell proliferation and differentiation through PTEN signaling. Stem Cell Reports. 2018 10:1193-1207.
  10. Qiao H, Li Y, Feng C, Duo S, Ji F, Jiao J*. Nap1l1 controls embryonic neural progenitor cell proliferation and differentiation in the developing brain. Cell Rep. 2018 22:2279-2293.
  11. Shen T, Ji F, Wang Y, Lei X, Zhang D, Jiao J*. Brain-specific deletion of histone variant H2A.z results in cortical neurogenesis defects and neurodevelopmental disorder. Nucleic Acids Res. 2018 46:2290-2307.
  12. Liang Q, Xia W, Li W, Jiao J*. RNF20 controls astrocytic differentiation through epigenetic regulation of STAT3 in the developing brain. Cell Death Differ. 2018 25:294-306.
  13. Li Y, Jiao J*. Histone chaperone HIRA regulates neural progenitor cell proliferation and neurogenesis via β-catenin. J Cell Biol. 2017 216:1975-1992.
  14. Xia W, Jiao J*. Histone variant H3.3 orchestrates neural stem cell differentiation in the developing brain. Cell Death Differ. 2017 24:1548-1563.
  15. Ji F, Shen T, Zou W, Jiao J*. UCP2 regulates embryonic neurogenesis via ROS-Mediated Yap alternation in the developing neocortex. Stem Cells. 2017 35:1479-1492.
  16. Yan L, Li Y, Shi Z, Lu X, Ma J, Hu B, Jiao J*, Wang H*. The zinc finger E-box-binding homeobox 1 (Zeb1) promotes the conversion of mouse fibroblasts into functional neurons. J Biol Chem. 2017 292:12959-12970.
  17. Zhang J, Chen S, Zhang D, Shi Z, Li H, Zhao T, Hu B, Zhou Q, Jiao J*. Tet3-Mediated DNA demethylation contributes to the direct conversion of fibroblast to functional neuron. Cell Rep. 2016 17:2326–2339.
  18. Wang S, Liang Q, Qiao H, Li H, Shen T, Ji F, Jiao J*. DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7. Development. 2016 143:2732-2740.
  19. Jiang H, Lv X, Lei X, Yang Y, Yang X, Jiao J*. Immune regulator MCPIP1 modulates TET expression during early neocortical development. Stem Cell Reports. 2016 7:439-453.
  20. Shi Z, Zhang J, Chen S, Li Y, Lei X, Qiao H, Zhu Q, Hu B, Zhou Q, Jiao J*. Conversion of Fibroblasts to Parvalbumin Neurons by One Transcription Factor, Ascl1, and the Chemical Compound Forskolin. J Biol Chem. 2016 291:13560-13570.
  21. Shen T, Ji F, Yuan Z, Jiao J*. CHD2 is required for embryonic neurogenesis in the developing cerebral cortex. Stem Cells. 2015 33:1794-1806.
  22. Xia W, Liu Y, Jiao J*. GRM7 regulates embryonic neurogenesis via CREB and YAP. Stem Cell Reports. 2015 4:795-810.
  23. Lv X, Jiang H, Liu Y, Lei X, Jiao J*. MicroRNA-15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development. EMBO Rep. 2014 15:1305-1314.
  24. Wang S, Li B, Qiao H, Lv X, Liang Q, Shi Z, Xia W, Ji F, Jiao J*. Autophagy-related gene Atg5 is essential for astrocyte differentiation in the developing mouse cortex. EMBO Rep. 2014 15:1053-1061.
  25. Zhang J, Ji F, Liu Y, Lei X, Li H, Ji G, Yuan Z, Jiao J*. Ezh2 regulates adult hippocampal neurogenesis and memory. J Neurosci. 2014 34:5184-5199.
  26. Huang W, She L, Chang X, Yang R, Wang L, Ji H, Jiao J, Poo M. Protein kinase LKB1 regulates polarized dendriteformation of adult hippocampal newborn neurons. Proc Natl Acad Sci USA. 2014 111:469-474.
  27. Shi Z, Shen T, Liu Y, Huang Y, Jiao J*. Retinoic acid receptor gamma (Rarg) and nuclear receptor subfamily 5, group A, member 2 (Nr5a2) promote conversion of fibroblasts to functional neurons. J Biol Chem. 2014 289:6415-6428.
  28. Lv X, Jiang H, Li B, Liang Q, Wang S, Zhao Q, Jiao J*. The crucial role of Atg5 in cortical neurogenesis during early brain development. Sci Rep. 2014 4:6010.
  29. Meng F, Chen S, Miao Q, Zhou K, Lao Q, Zhang X, Guo W, Jiao J*. Induction of fibroblasts to neurons through adenoviral gene delivery. Cell Res. 2012 22:436-440.
  30. Jiao J, Feldheim DA, Chen DF. Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system. Proc Natl Acad Sci USA. 2008 105: 8778-8783.
  31. Jiao J, Chen DF. Induction of neurogenesis in non-conventional neurogenic regions of the adult CNS by niche astrocyte-produced signals, Stem Cells. 2008 26:1221-1230.
  32. Jiao J, Huang X, Feit-Leithman RA, Neve RL, Snider W, Dartt DA, Chen DF. Bcl-2 enhances Ca2+ signaling to support the intrinsic regenerative capacity of CNS axons. EMBO J. 2005 24:1068-1078.