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.

2007.9-2010.6, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Ph.D. in Cell Biology, Mentor Dr. Duanqing Pei, thesis “Effect and Mechanism of Vitamin C in Generation of Induced Pluripotent Stem Cells”.

1994.9-1998.6, College of Life Sciences, Peking University, B.S. in Biochemistry and Molecular Biology.

2013.9-current, GIBH, CAS, Principal Investigator

2010.7-2013.8, GIBH, CAS, Associate Principal Investigator

2004.9-2007.8, GIBH, CAS, Research Associate

2002.2-2004.8, Medical School, Tsinghua University, Research Assistant

1999.2-2002.1, Fuwai Heart Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Research Assistant

^#Corresponding author

^* First author

1-Wu Y, Li Y, Zhang H, Huang Y, Zhao P, Tang Y, Qiu X, Ying Y, Li W, Ni S, Zhang M, Liu L, Xu Y, Zhuang Q, Luo Z, Benda C, Song H, Liu B, Lai L, Liu X, Tse HF, Bao X, Chan WY, Esteban MA, Qin B^#, Pei D^#.(2015) Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming. Nature Cell Biology, 17: 715-725.

2-Su J, Pei D, Qin B^#. (2013) Roles of small molecules in somatic cell reprogramming. Acta Pharmacologica Sinica34:719–24.

3-Bao X, Zhu X, Liao B, Benda C, Zhuang Q, Pei D, Qin B^#, Esteban MA^#.(2013) MicroRNAs in somatic cell reprogramming. Current Opinion in Cell Biology25(2):208-14.

4-Esteban MA^*, Wang T^*, Qin B^*, Yang J, Qin D, Cai J, Li W, Weng Z, Chen J, Ni S, Chen K, Li Y, Liu X, Xu J, Zhang S, Li F, He W, Labuda K, Song Y, Peterbauer A, Wolbank S, Redl H, Zhong M, Cai D, Zeng L, Pei D. (2010) Vitamin C Enhances the Generation of Mouse and Human Induced Pluripotent Stem Cells. Cell Stem Cell6:1–9. (Cover story)

5-Qin B^*, He M, Chen X, Pei D.(2006) Sorting Nexin 10 Induces Giant Vacuoles in Mammalian Cells. Journal of Biological Chemistry281 (48): 36891-6. (Cover story)

6-Qin B^*, Chen X, Zhu J, Pei D.(2005) Identification of EGFR kinase domain mutations among lung cancer patients in China: implication for targeted cancer therapy. Cell Research 15 (3): 212-7.

7-Cui P^*, Qin B^*, Liu N, Pan G, Pei D.(2004) Nuclear localization of the phosphatidylserine receptor protein via multiple nuclear localization signals.Experimental Cell Research293: 154-63.

8-Bao X, Guo X, Yin M, Tariq M, Lai Y, Kanwal S, Zhou J, Li N, Lv Y, Pulido-Quetglas C, Wang X, Ji L, Khan MJ, Zhu X, Luo Z, Shao C, Lim DH, Liu X, Li N, Wang W, He M, Liu YL, Ward C, Wang T, Zhang G, Wang D, Yang J, Chen Y, Zhang C, Jauch R, Yang YG, Wang Y, Qin B, Anko ML, Hutchins AP, Sun H, Wang H, Fu XD, Zhang B, Esteban MA.(2018) Capturing the interactome of newly transcribed RNA. Nature Methods15(3): 213-220.

9-Zhuang Q, Li W, Benda C, Huang Z, Ahmed T, Liu P, Guo X, Ibañez DP, Luo Z, Zhang M, Abdul MM, Yang Z, Yang J, Huang Y, Zhang H, Huang D, Zhou J, Zhong X, Zhu X, Fu X, Fan W, Liu Y, Xu Y, Ward C, Khan MJ, Kanwal S, Mirza B, Tortorella MD, Tse HF, Chen J, Qin B, Bao X, Gao S, Hutchins AP, Esteban MA.NCoR / SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming. Nature Cell Biology20(4): 400-412.

10-Li L, Zhang Q, Yang H, Zou Q, Lai C, Jiang F, Zhao P, Luo Z, Yang J, Chen Q, Wang Y, Newsome PN, Li W, Chen S, Wang D, Siu TS, Tam S, Tse HF, Qin B, Bao X, Esteban MA, Lai L.(2017) Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1. Journal of Biological Chemistry292:4755–4763. 

11-Yang J, Wang Y, Zhou T, Wong LY, Tian XY, Hong X, Lai WH, Au KW, Wei R, Liu Y, Chen LH, Liang G, Huang Z, Fan W, Zhao P, Wang X, Ibanez DP, Luo Z, Li Y, Zhong X, Chen S, Wang D, Li L, Lai L, Qin B, Bao X, Hutchins AP, Siu CW, Huang Y, Esteban MA, Tse HF. (2017) Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells. Stem Cell Reports8:605–618. 

12-Xu Y, Zhang M, Li W, Zhu X, Bao X, Qin B, Hutchins AP, Esteban MA.(2016) Transcriptional Control of Somatic Cell Reprogramming. Trends in Cell Biology26:272–288.

13-Bao X, Wu H, Zhu X, Guo X, Hutchins AP, Luo Z, Song H, Chen Y, Lai K, Yin M, Xu L, Zhou L, Chen J, Wang D, Qin B, Frampton J, Tse HF, Pei D, Wang H, Zhang B, Esteban MA.(2014) The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters. Cell Research25:80–92. 

14-Liu L, Xu Y, He M, Zhang M, Cui F, Lu L, Yao M, Tian W, Benda C, Zhuang Q, Huang Z, Li W, Li X, Zhao P, Fan W, Luo Z, Li Y, Wu Y, Hutchins AP, Wang D, Tse HF, Schambach A, Frampton J, Qin B, Bao X, Yao H, Zhang B, Sun H, Pei D, Wang H, Wang J, Esteban MA.(2014) Transcriptional pause release is a rate-limiting step for somatic cell reprogramming. Cell Stem Cell15:574–588. 

15-Zhuang Q, Qing X, Ying Y, Wu H, Benda C, Lin J, Huang Z, Liu L, Xu Y, Bao X, Qin B, Pei D, Esteban MA.(2013) Class IIa histone deacetylases and myocyte enhancer factor 2 proteins regulate the mesenchymal-to-epithelial transition of somatic cell reprogramming. Journal of Biological Chemistry288:12022–12031. 

16-Esteban MA, Bao X, Zhuang Q, Zhou T, Qin B, Pei D.(2012) The mesenchymal-to-epithelial transition in somatic cell reprogramming. Current Opinion in Genetics & Development22:423–428. 

17-Wang T, Chen K, Zeng X, Yang J, Wu Y, Shi X,Qin B, Zeng L, Esteban MA, Pan G, Pei D.(2011) The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner. Cell Stem Cell9:575–587.

18-Liao B, Bao X, Liu L, Feng S, Zovoilis A, Liu W, Xue Y, Cai J, Guo X, Qin B, Zhang R, Wu J, Lai L, Teng M, Niu L, Zhang B, Esteban MA, Pei D.(2011) MicroRNA cluster 302-367 enhances somatic cell reprogramming by accelerating a mesenchymal-to-epithelial transition. Journal of Biological Chemistry286:17359–17364. 

19-Li R, Liang J, Ni S, Zhou T, Qing X, Li H, He W, Chen J, Li F, Zhuang Q, Qin B, Xu J, Li W, Yang J, Gan Y, Qin D, Feng S, Song H, Yang D, Zhang B, Zeng L, Lai L, Esteban MA, Pei D.(2010) A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell7:51–63. 

20-Yao D, Wu B, Qin B, Pei D(2009) PX domain and CD domain play different roles in localization and vacuolation of Sorting Nexin 10. Chinese Science Bulletin54:3965–3971. 

21-Pan G, Qin B, Liu N, Scholer HR, Pei D.(2004) Identification of a nuclear localization signal in OCT4 and generation of a dominant negative mutant by its ablation. Journal of Biological Chemistry279:37013–37020.

1, “Application of vitamin C in generation of iPSCs and culture of embryonic stem cells”, 2009, application No. 200910041331.9

2, “Application of sorting nexin 10 in inhibiting cancer cell growth”, 2006, application No. 200610036692.0

3, “Application of mutants of EGFR genes”, 2005, application No. 200510115906.9

1, “Roles and mechanisms of metabolism, autophagy and DNA damage repair in maintaining stemness and genome stability of pluripotent stem cells”, the National Key R&D Program of China, Stem Cell and Translational Research, 2016.7-2020.12, Grant No. 2016YFA0100300, RMB 28,580,000, chief scientist and project No. 1 leader.

2, “Roles and mechanisms of p62 and Nrf2 in embryonic stem cell and somatic cell reprogramming”, the National Natural Science Foundation of China, 2016.1-2019.12, Grant No. 31571524, RMB 770,000, project leader.

3, “Using Parkinson’s disease iPSCs to model aging related heart diseases”, the Guangdong Provincial Science and Technology Program, 2016.1-2017.12, Grant No. 2016A050503037, RMB 1,000,000, project leader.

4, “Impact and mechanism of senescence memory on somatic cell reprogramming”, the Guangdong Provincial Key Basic Research Program, 2015.8-2019.8, Grant No. 2015A030308007, RMB 1,000,000, project leader.

5, “Establishment and application of the optimized mesenchymal stem cells from induced pluripotent stem cells”, the Guangzhou International Collaboration Program, 2015.1-2016.12, Grant No. 201508030027, RMB 2,000,000, project leader.

6, “Establishment of safe and high efficient iPSC technology through modulating nc-RNAs”, the National Basic Research Program of China (973 Program), 2011.1-2015.12, Grant No. 2011CBA01106, RMB 4,350,000, project No. 6 participant.

7, “Generation of organ deficient miniature pigs”, the National Basic Research Program of China (973 Program), 2011.1-2015.12, Grant No. 2011CBA01004, RMB 6,730,000, project No. 4 leader.

8, “Regulation of endosome homeostasis by sorting nexin 10 and 11”, the National Natural Science Foundation of China, 2008.1-2010.12, Grant No. 30700410, RMB 200,000, project leader.

9, “Study of EGFR trafficking by sorting nexins”, the Guangdong Provincial Natural Science Foundation, 2005.8-2006.12, Grant No. 05014036, RMB 80,000, project leader.

“Mitochondrial Remodeling in Somatic Reprogramming”, the 8th Guangzhou International Conference on Stem Cell and Regenerative Medicine, lecture, 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  

Ph.D. graduates: Yinghua Huang, Hui Zhang, Yasong Wu, Yuan Li.

Ph.D. candidate: Lulu Wang.

M.S. candidates: Gang Ma, Chuanqing Tang, Runxia Lin, Xueting Xu.