My lab studies how to control stem cell fate through modulating the two interconnected layers, metabolism and epigenetics. 

 

In around 2009, the ground-breaking induced pluripotent stem cell technology was very low efficient and we aimed to improve it through understanding how it works. Knowing the difference in metabolism between somatic and embryonic stem (ES) cell, we first postulated that mitochondrial reactive oxygen species (ROS) might inhibit reprogramming. We tested a spectrum of antioxidants and identified only vitamin C could (Vc) dramatically enhance reprogramming efficiency, independent of its well-known antioxidant activity. Actually, Vc can activate a group of histone and DNA demethylases to remove epigenetic barriers in somatic cells and during reprogramming. Until today, the roles of only a few demethylases and their targets in reprogramming, stem cell and development have been clarified but a lot more others await future exploration. 

 

Recently, we asked how the whole intercellular organelle system is remodeled during somatic cell reprogramming. Initially we postulated that autophagy may mediate this cellular remodeling. Surprisingly however, we discovered that it’s not autophagy but its upstream repressor, mTORC1, that regulates cytoarchitecture through mitochondrial biosynthesis. Autophagy and mTORC1 are evolutionarily conserved metabolic regulators and in vivo studies support their important roles in stem cell maintenance and aging. How exactly they function, be regulated and linked to epigenetic state of stem cells are still largely unknown and very important issues.

We believe understanding deeper how mTORC1 and autophagy control the metabolic and epigenetic state of stem cell may provide us new important clues for how to promote longevity.

2007-09--2010-07   中科院广州生物医药与健康研究院   博士
1994-09--1998-06   北京大学生命科学学院   本科

   

2013-09~2017-08,中科院广州生物医药与健康研究员, 研究员
2010-07~2013-08,中国科学院广州生物医药与健康研究院, 副研究员

   

（1） 广东省“特支计划”科技创新领军人才, 省级, 2016
（2） 干细胞多能性与重编程机理研究, 二等奖, 国家级, 2013
（3） 中国科学院百篇优秀博士学位论文, , 院级, 2011
（4） 中国科学院院长优秀奖, , 院级, 2010
（5） 中国科学院优秀毕业生, , 院级, 2010

（ 1 ） 分选蛋白SNX10抑制肿瘤细胞生长的用途, 发明, 2006, 第 2 作者, 专利号: 200610036692.0
（ 2 ） 人表皮生长因子受体突变基因及其用途, 发明, 2005, 第 2 作者, 专利号: 200510115906.9
（ 3 ） 抗坏血酸在诱导多能干细胞制备和胚胎干细胞培养的应用, 发明, 2009, 第 4 作者, 专利号: 200910041331.9

   

（1） NCoR/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming, Nature Cell Biology, 2018, 其他（合作组作者）
（2） Capturing the interactome of newly transcribed RNA, Nature Methods, 2018, 其他（合作组作者）
（3） Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1, Journal of Biological Chemistry, 2017, 其他（合作组作者）
（4） Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells, Stem Cell Reports, 2017, 其他（合作组作者）
（5） Transcriptional Control of Somatic Cell Reprogramming, Trends in Cell Biology, 2016, 第 6 作者
（6） Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming, Nature Cell Biology, 2015, 通讯作者
（7） The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters, Cell Research, 2014, 其他（合作组作者）
（8） Transcriptional Pause Release Is a Rate-Limiting Step for Somatic Cell Reprogramming, Cell Stem Cell, 2014, 其他（合作组作者）
（9） MicroRNAs in somatic cell reprogramming, Current Opinion in Cell Biology, 2013, 通讯作者
（10） Roles of small molecules in somatic cell reprogramming, Acta Pharmacologica Sinica, 2013, 通讯作者
（11） The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner, Cell Stem Cell, 2013, 第 7 作者
（12） Class IIa Histone Deacetylases and MEF2 proteins Regulate the Mesenchymal-to-Epithelial Transition of Somatic Cell Reprogramming, Journal of Biological Chemistry, 2013, 其他（合作组作者）
（13） The mesenchymal-to-epithelial transition in somatic cell reprogramming, Current Opinion in Genetics and Development, 2012, 第 5 作者
（14） MicroRNA Cluster 302–367 Enhances Somatic Cell Reprogramming by Accelerating a Mesenchymal-to- Epithelial Transition, Journal of Biological Chemistry, 2011, 其他（合作组作者）
（15） Vitamin C Enhances the Generation of Mouse and Human Induced Pluripotent Stem Cells, Cell Stem Cell, 2010, 第 1 作者
（16） A Mesenchymal-to-Epithelial Transition Initiates and Is Required for the Nuclear Reprogramming of Mouse Fibroblasts, Cell Stem Cell, 2010, 其他（合作组作者）
（17） Sorting Nexin 10 Induces Giant Vacuoles in Mammalian Cells, Journal of Biological Chemistry, 2006, 第 1 作者
（18） Identification of EGFR kinase domain mutations among lung cancer patients in China: implication for targeted cancer therapy, Cell Research, 2005, 第 1 作者
（19） Nuclear localization of the phosphatidylserine receptor protein via multiple nuclear localization signals, Experimental Cell Research, 2004, 第 1 作者
（20） Identification of a Nuclear Localization Signal in OCT4 and Generation of a Dominant Negative Mutant by Its Ablation, Journal of Biological Chemistry, 2004, 第 2 作者

   

（ 1 ） 诱导多能干细胞（iPs）猪与小型猪疾病模型, 主持, 国家级, 2011-01--2015-12
（ 2 ） 非编码RNA在干细胞命运调控中的功能及分子机制, 参与, 国家级, 2011-01--2015-12
（ 3 ） p62和Nrf2在胚胎干细胞自我更新和体细胞重编程中的作用和机制研究, 主持, 国家级, 2016-01--2019-12
（ 4 ） 代谢、自噬和DNA损伤修复协同维持多能干细胞干性和染色体稳定性的机理研究, 主持, 国家级, 2016-07--2020-12
（ 5 ） 利用帕金森病iPS细胞研究衰老相关心肌病的发病机理及其应用, 主持, 省级, 2016-01--2017-12
（ 6 ） 衰老记忆对体细胞重编程的影响和机制研究, 主持, 省级, 2015-08--2019-08
（ 7 ） 具有优越免疫调节活性的诱导多能性干细胞(iPSCs)来源的间充质干细胞的获得及应用研究, 主持, 省级, 2015-01--2016-12
（ 8 ） SNX10和SNX11对内涵体形态发生的调节机制研究, 主持, 国家级, 2008-01--2010-12
（ 9 ） 分选蛋白SNX对EGFR转运调控机制的影响, 主持, 省级, 2005-08--2006-12

（1）Mitochondrial Remodeling in Somatic Reprogramming   2015-12-19

已指导学生

吴亚松  博士研究生  071010-生物化学与分子生物学  

张辉  博士研究生  071010-生物化学与分子生物学  

黄颖华  博士研究生  071010-生物化学与分子生物学  

现指导学生

王璐璐  博士研究生  071010-生物化学与分子生物学  

林润霞  博士研究生  071010-生物化学与分子生物学  

姜澈  硕士研究生  071009-细胞生物学