Chemical screen identifies a geroprotective role of quercetin in premature aging

doi:10.1007/s13238-018-0567-y

Protein Cell

2019, Vol. 10

Issue (6) : 417-435 https://doi.org/10.1007/s13238-018-0567-y

RESEARCH ARTICLE

Chemical screen identifies a geroprotective role of quercetin in premature aging

Lingling Geng^1,², Zunpeng Liu^3,⁵, Weiqi Zhang^1,^2,⁵(

), Wei Li^1,³, Zeming Wu^3,⁵, Wei Wang^2,⁵, Ruotong Ren^2,⁵, Yao Su¹, Peichang Wang¹, Liang Sun⁸, Zhenyu Ju⁷, Piu Chan^1,⁵, Moshi Song^4,^5,⁶(

), Jing Qu^3,^5,⁶(

), Guang-Hui Liu^1,^2,^5,^6,⁷(

)

¹. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
². National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
³. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
⁴. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
⁵. University of Chinese Academy of Sciences, Beijing 100049, China
⁶. Institute of Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
⁷. Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China
⁸. The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, China

Download: PDF(4299 KB)
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

Keywords Quercetin Stem cell Aging Werner syndrome Hutchinson-Gilford progeria syndrome

Corresponding Author(s): Weiqi Zhang,Moshi Song,Jing Qu,Guang-Hui Liu

Issue Date: 19 June 2019

Cite this article:

Lingling Geng,Zunpeng Liu,Weiqi Zhang, et al. Chemical screen identifies a geroprotective role of quercetin in premature aging[J]. Protein Cell, 2019, 10(6): 417-435.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-018-0567-y
https://academic.hep.com.cn/pac/EN/Y2019/V10/I6/417

1	S Anders, PT Pyl, W Huber (2015) HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics 31:166–169 https://doi.org/10.1093/bioinformatics/btu638
2	B Ansgar (2013) Inhibition of mTOR Signaling by Quercetin in Cancer Treatment and Prevention. Anticancer Agents Med Chem 13:1025–1031 https://doi.org/10.2174/18715206113139990114
3	E Bahar, J-Y Kim, H Yoon (2017) Quercetin Attenuates Manganese-Induced Neuroinflammation by Alleviating Oxidative Stress through Regulation of Apoptosis, iNOS/NF-κB and HO-1/Nrf2 Pathways. Int J Mol Sci 18:1989 https://doi.org/10.3390/ijms18091989
4	BA Benayoun, EA Pollina, A Brunet (2015) Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat Rev Mol Cell Biol 16:593–610 https://doi.org/10.1038/nrm4048
5	CR Burtner, BK Kennedy (2010) Progeria syndromes and ageing: what is the connection? Nature Reviews Molecular Cell Biology 11:567 https://doi.org/10.1038/nrm2944
6	J Campisi (2013) Aging, Cellular Senescence, and Cancer. Annual review of physiology 75:685–705 https://doi.org/10.1146/annurev-physiol-030212-183653
7	J Chang, Y Wang, L Shao, R-M Laberge, M Demaria, J Campisi, K Janakiraman, NE Sharpless, S Ding, W Fenget al. (2016) Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nature medicine 22:78–83 https://doi.org/10.1038/nm.4010
8	J Chen, EE Bardes, BJ Aronow, AG Jegga (2009) ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucl Acids Res 37:W305–W311 https://doi.org/10.1093/nar/gkp427
9	KH Chiow, MC Phoon, T Putti, BKH Tan, VT Chow (2016) Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection. Asian Pacific Journal of Tropical Medicine 9:1–7 https://doi.org/10.1016/j.apjtm.2015.12.002
10	N Chondrogianni, S Kapeta, I Chinou, K Vassilatou, I Papassideri, ES Gonos (2010) Anti-ageing and rejuvenating effects of quercetin. Experimental Gerontology 45:763–771 https://doi.org/10.1016/j.exger.2010.07.001
11	Y Dai, H Zhang, J Zhang, M Yan (2018) Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NFkappaB pathway. Chem Biol Interact 284:32–40 https://doi.org/10.1016/j.cbi.2018.02.017
12	G Darband Saber, M Kaviani, B Yousefi, S Sadighparvar, G Pakdel Firouz, A Attari Javad, I Mohebbi, S Naderi, M Majidinia (2018) Quercetin: A functional dietary flavonoid with potential chemopreventive properties in colorectal cancer. Journal of Cellular Physiology 233:6544–6560 https://doi.org/10.1002/jcp.26595
13	F Debacq-Chainiaux, JD Erusalimsky, J Campisi, O Toussaint (2009) Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protoc 4:1798–1806 https://doi.org/10.1038/nprot.2009.191
14	S Duan, G Yuan, X Liu, R Ren, J Li, W Zhang, J Wu, X Xu, L Fu, Y Li (2015) PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype. Nature Communications 6:10068 https://doi.org/10.1038/ncomms10068
15	J Fang, J Yang, X Wu, G Zhang, T Li, X Wang, H Zhang, C Wang, G-H Liu, L Wang (2018) Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7. Aging Cell 17(4):e12765 https://doi.org/10.1111/acel.12765
16	L Fu, X Xu, R Ren, J Wu, W Zhang, J Yang, X Ren, S Wang, Y Zhao, L Sunet al. (2016) Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs. Protein & Cell 7:210–221 https://doi.org/10.1007/s13238-016-0244-y
17	W Gao, L Pu, M Chen, J Wei, Z Xin, Y Wang, Z Yao, T Shi, C Guo (2018) Glutathione homeostasis is significantly altered by quercetin via the Keap1/Nrf2 and MAPK signaling pathways in rats. Journal of Clinical Biochemistry and Nutrition 62:56–62 https://doi.org/10.3164/jcbn.17-40
18	K Griffiths, BB Aggarwal, RB Singh, HS Buttar, D Wilson, F De Meester (2016) Food Antioxidants and Their Anti-Inflammatory Properties: A Potential Role in Cardiovascular Diseases and Cancer Prevention. Diseases 4:28 https://doi.org/10.3390/diseases4030028
19	K Harhouri, D Frankel, C Bartoli, P Roll, A De Sandre-Giovannoli, N Lévy (2018) An overview of treatment strategies for Hutchinson-Gilford Progeria Syndrome. Nucleus 9(1):246–257 https://doi.org/10.1080/19491034.2018.1460045
20	CB Harley (1991) Telomere loss: mitotic clock or genetic time bomb? Mutation Research 256:271–282 https://doi.org/10.1016/0921-8734(91)90018-7
21	CM Hennekam Raoul (2006) Hutchinson-Gilford progeria syndrome: Review of the phenotype. American Journal of Medical Genetics Part A 140A:2603–2624 https://doi.org/10.1002/ajmg.a.31346
22	A Kampkötter, C Timpel, RF Zurawski, S Ruhl, Y Chovolou, P Proksch, W Wätjen (2008) Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 149:314–323 https://doi.org/10.1016/j.cbpb.2007.10.004
23	D Kim, B Langmead, SL Salzberg (2015) HISAT: a fast spliced aligner with low memory requirements. Nature methods 12:357–360 https://doi.org/10.1038/nmeth.3317
24	Y Kim, CS Kim, Y Joe, HT Chung, TY Ha, R Yu (2018) Quercetin Reduces Tumor Necrosis Factor Alpha-Induced Muscle Atrophy by Upregulation of Heme Oxygenase-1. Journal of medicinal food 21:551–559 https://doi.org/10.1089/jmf.2017.4108
25	R Kreienkamp, M Croke, MA Neumann, G Bedia-Diaz, S Graziano, A Dusso, D Dorsett, C Carlberg, S Gonzalo (2016) Vitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes. Oncotarget 7:30018–30031 https://doi.org/10.18632/oncotarget.9065
26	N Kubben, W Zhang, L Wang, TC Voss, J Yang, J Qu, GH Liu, T Misteli (2016) Repression of the antioxidant NRF2 pathway in premature aging. Cell 165(6):1361–1374 https://doi.org/10.1016/j.cell.2016.05.017
27	BA Kudlow, BK Kennedy, RJ Jr Monnat (2007) Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nature Reviews Molecular Cell Biology 8:394 https://doi.org/10.1038/nrm2161
28	C López-Otín, MA Blasco, L Partridge, M Serrano, G Kroemer (2013) The Hallmarks of Aging. Cell 153:1194–1217 https://doi.org/10.1016/j.cell.2013.05.039
29	A Labbé, RV Turaga, ER Paquet, C Garand, M Lebel (2010) Expression profiling of mouse embryonic fibroblasts with a deletion in the helicase domain of the Werner Syndrome gene homologue treated with hydrogen peroxide. Bmc Genomics 11:127 https://doi.org/10.1186/1471-2164-11-127
30	M Lebel (2001) Werner syndrome: genetic and molecular basis of a premature aging disorder. Cellular and molecular life sciences: CMLS 58:857–867 https://doi.org/10.1007/s00018-001-8398-y
31	Y Li, J Yao, C Han, J Yang, MT Chaudhry, S Wang, H Liu, Y Yin (2016a) Quercetin. Inflammation and Immunity. Nutrients 8:167 https://doi.org/10.3390/nu8030167
32	Y Li, W Zhang, L Chang, Y Han, L Sun, X Gong, H Tang, Z Liu, H Deng, Y Yeet al. (2016b) Vitamin C alleviates aging defects in a stem cell model for Werner syndrome. Protein & Cell 7:478–488 https://doi.org/10.1007/s13238-016-0278-1
33	GH Liu, BZ Barkho, S Ruiz, D Diep, J Qu, S-L Yang, AD Panopoulos, K Suzuki, L Kurian, C Walshet al. (2011a) Recapitulation of premature aging with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472:221–225 https://doi.org/10.1038/nature09879
34	GH Liu, K Suzuki, J Qu, I Sancho-Martinez, F Yi, M Li, S Kumar, E Nivet, J Kim, RD Soligallaet al. (2011b) Targeted Gene Correction of Laminopathy-Associated LMNA Mutations in Patient-Specific iPSCs. Cell stem cell 8:688–694 https://doi.org/10.1016/j.stem.2011.04.019
35	W Liu, M Zhang, J Feng, A Fan, Y Zhou, Y Xu (2017) The Influence of Quercetin on Maternal Immunity, Oxidative Stress, and Inflammation in Mice with Exposure of Fine Particulate Matter during Gestation. International Journal of Environmental Research and Public Health 14:592 https://doi.org/10.3390/ijerph14060592
36	DB Lombard, KF Chua, R Mostoslavsky, S Franco, M Gostissa, FW Alt (2005) DNA Repair, Genome Stability, and Aging. Cell 120:497–512 https://doi.org/10.1016/j.cell.2005.01.028
37	MI Love, W Huber, S Anders (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome biology 15:550 https://doi.org/10.1186/s13059-014-0550-8
38	I Murfuni, AD Santis, M Federico, M Bignami, P Pichierri, A Franchitto (2012) Perturbed replication induced genome wide or at common fragile sites is differently managed in the absence of WRN. Carcinogenesis 33:1655 https://doi.org/10.1093/carcin/bgs206
39	M Ogrodnik, S Miwa, T Tchkonia, D Tiniakos, CL Wilson, A Lahat, CP Day, A Burt, A Palmer, QM Ansteeet al. (2017) Cellular senescence drives age-dependent hepatic steatosis. Nature Communications 8:15691 https://doi.org/10.1038/ncomms15691
40	PL Opresko, WH Cheng, C von Kobbe, JA Harrigan, VA Bohr (2003) Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis 24:791–802 https://doi.org/10.1093/carcin/bgg034
41	A Ozgenc, LA Loeb (2006) Werner Syndrome, aging and cancer. Genome dynamics 1:206–217 https://doi.org/10.1159/000092509
42	H Pan, D Guan, X Liu, J Li, L Wang, J Wu, J Zhou, W Zhang, R Ren, W Zhang (2016) SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Research 26:190–205 https://doi.org/10.1038/cr.2016.4
43	J Polosak, A Kurylowicz, M Roszkowska-Gancarz, M Owczarz, M Puzianowska-Kuznicka (2011) Aging is accompanied by a progressive decrease of expression of the WRN gene in human blood mononuclear cells. Journals of Gerontology 66:19 https://doi.org/10.1093/gerona/glq162
44	R Ren, L Deng, Y Xue, K Suzuki, W Zhang, Y Yu, J Wu, L Sun, X Gong, H Luan (2017a) Visualization of aging-associated chromatin alterations with an engineered TALE system. Cell Research 27:483–504 https://doi.org/10.1038/cr.2017.18
45	R Ren, A Ocampo, GH Liu, JC Izpisua Belmonte (2017b) Regulation of Stem Cell Aging by Metabolism and Epigenetics. Cell metabolism 26:460–474 https://doi.org/10.1016/j.cmet.2017.07.019
46	X Ren, S Lim, Z Ji, J Yuh, V Peng, MT Smith, L Zhang (2011) Comparison of Proliferation and Genomic Instability Responses to WRN Silencing in Hematopoietic HL60 and TK6 Cells. Plos One 6:e14546 https://doi.org/10.1371/journal.pone.0014546
47	E Reszka, E Wieczorek, E Jablonska, B Janasik, W Fendler, W Wasowicz (2015) Association between plasma selenium level and NRF2 target genes expression in humans. Journal of Trace Elements in Medicine and Biology 30:102–106 https://doi.org/10.1016/j.jtemb.2014.11.008
48	C Salvatore (2010) The Role of Quercetin, Flavonols and Flavones in Modulating Inflammatory Cell Function. Inflammation & Allergy- Drug Targets (Discontinued) 9:263–285 https://doi.org/10.2174/187152810793358741
49	M Seki, M Otsuki, Y Ishii, S Tada, T Enomoto (2008) RecQ family helicases in genome stability: lessons from gene disruption studies in DT40 cells. Cell Cycle 7:2472–2478 https://doi.org/10.4161/cc.7.16.6462
50	RA Shamanna, DL Croteau, JH Lee, VA Bohr (2017) Recent advances in understanding werner syndrome. F1000research 6:1779 https://doi.org/10.12688/f1000research.12110.1
51	JR Smith, OM Pereirasmith (1996) Replicative Senescence: Implications for in Vivo Aging and Tumor Suppression. Science 273:63–67 https://doi.org/10.1126/science.273.5271.63
52	E-J Sohn, JM Kim, S-H Kang, J Kwon, HJ An, J-S Sung, KA Cho, I-S Jang, J-S Choi (2018) Restoring effects of natural anti-oxidant quercetin on cellular senescent human dermal fibroblasts. Am J Chin Med 46(4):1–21 https://doi.org/10.1142/S0192415X18500453
53	D Szklarczyk, JH Morris, H Cook, M Kuhn, S Wyder, M Simonovic, A Santos, NT Doncheva, A Roth, P Borket al. (2017) The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucl Acids Res 45:D362–D368 https://doi.org/10.1093/nar/gkw937
54	R Tacutu, T Craig, A Budovsky, D Wuttke, G Lehmann, D Taranukha, J Costa, VE Fraifeld, JP de Magalhaes (2013) Human Ageing Genomic Resources: integrated databases and tools for the biology and genetics of ageing. Nucleic Acids Res 41:D1027–1033 https://doi.org/10.1093/nar/gks1155
55	A Uccelli, L Moretta, V Pistoia (2008) Mesenchymal stem cells in health and disease. Nature reviews Immunology 8:726–736 https://doi.org/10.1038/nri2395
56	N Ullrich, L Gordon (2015) Chapter 18- Hutchinson–Gilford progeria syndrome. In: Islam MP, Roach ES (eds) Neurocutaneous Syndromes. Handbook of Clinical Neurology, vol 132. Elsevier, pp 249–264 https://doi.org/10.1016/B978-0-444-62702-5.00018-4
57	B Villeponteau (1997) The heterochromatin loss model of aging. Experimental Gerontology 32:383–394 https://doi.org/10.1016/S0531-5565(96)00155-6
58	P Wang, Z Liu, X Zhang, J Li, L Sun, Z Ju, J Li, P Chan, G-H Liu, W Zhanget al. (2018a) CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells. Protein Cell. https://doi.org/10.1007/s13238-018-0560-5
59	S Wang, B Hu, Z Ding, Y Dang, J Wu, D Li, X Liu, B Xiao, W Zhang, R Renet al. (2018b) ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells. Cell Discovery 4:2 https://doi.org/10.1038/s41421-017-0003-0
60	Z Wu, W Zhang, M Song, W Wang, G Wei, W Li, J Lei, Y Huang, Y Sang, P Chanet al. (2018) Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome. Protein & Cell 9:333–350 https://doi.org/10.1007/s13238-018-0517-8
61	Z Xu, W Feng, Q Shen, N Yu, K Yu, S Wang, Z Chen, S Shioda, Y Guo (2017) Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation. Aging and Disease 8:760–777 https://doi.org/10.14336/AD.2016.0620
62	J Yang, N Cai, F Yi, GH Liu, J Qu, JC Izpisua Belmonte (2014) Gating pluripotency via nuclear pores. Trends in molecular medicine 20:1–7 https://doi.org/10.1016/j.molmed.2013.10.003
63	J Yang, J Li, K Suzuki, X Liu, J Wu, W Zhang, R Ren, W Zhang, P Chan, JC Izpisua Belmonteet al. (2017) Genetic enhancement in cultured human adult stem cells conferred by a single nucleotide recoding. Cell Res 27:1178–1181 https://doi.org/10.1038/cr.2017.86
64	CE Yu, J Oshima, YH Fu, EM Wijsman, F Hisama, R Alisch, S Matthews, J Nakura, T Miki, S Ouais (1996) Positional cloning of the Werner’s syndrome gene. Science 272:258–262 https://doi.org/10.1126/science.272.5259.258
65	QC Yu, W Song, D Wang, YA Zeng (2016) Identification of blood vascular endothelial stem cells by the expression of protein C receptor. Cell Research 26:1079–1098 https://doi.org/10.1038/cr.2016.85
66	W Zhang, J Li, K Suzuki, J Qu, P Wang, J Zhou, X Liu, R Ren, X Xu, A Ocampoet al. (2015) A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science (New York, NY) 348:1160–1163 https://doi.org/10.1126/science.aaa1356
67	M Zhou, S Wang, A Zhao, K Wang, Z Fan, H Yang, W Liao, S Bao, L Zhao, Y Zhanget al. (2012) Transcriptomic and Metabonomic Profiling Reveal Synergistic Effects of Quercetin and Resveratrol Supplementation in High Fat Diet Fed Mice. Journal of Proteome Research 11:4961–4971 https://doi.org/10.1021/pr3004826
68	Y Zhu, T Tchkonia, T Pirtskhalava, AC Gower, H Ding, N Giorgadze, AK Palmer, Y Ikeno, GB Hubbard, M Lenburget al. (2015) The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14:644–658 https://doi.org/10.1111/acel.12344

[1]

PAC-0417-18307-LGH_suppl_1

Download

[1]	Ermin Li, Xiuya Li, Jie Huang, Chen Xu, Qianqian Liang, Kehan Ren, Aobing Bai, Chao Lu, Ruizhe Qian, Ning Sun. BMAL1 regulates mitochondrial fission and mitophagy through mitochondrial protein BNIP3 and is critical in the development of dilated cardiomyopathy[J]. Protein Cell, 2020, 11(9): 661-679.
[2]	Kun Liu, Jiani Cao, Xingxing Shi, Liang Wang, Tongbiao Zhao. Cellular metabolism and homeostasis in pluripotency regulation[J]. Protein Cell, 2020, 11(9): 630-640.
[3]	Shijia Bi, Zunpeng Liu, Zeming Wu, Zehua Wang, Xiaoqian Liu, Si Wang, Jie Ren, Yan Yao, Weiqi Zhang, Moshi Song, Guang-Hui Liu, Jing Qu. SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer[J]. Protein Cell, 2020, 11(7): 483-504.
[4]	Jianwei Liu, Mengdi Wang, Le Sun, Na Clara Pan, Changjiang Zhang, Junjing Zhang, Zhentao Zuo, Sheng He, Qian Wu, Xiaoqun Wang. *Integrative analysis of in vivo* recording with single-cell RNA-seq data reveals molecular properties of light-sensitive neurons in mouse V1**[J]. Protein Cell, 2020, 11(6): 417-432.
[5]	Yunxiang Yang, Pan Yang, Nan Wang, Zhonghao Chen, Dan Su, Z. Hong Zhou, Zihe Rao, Xiangxi Wang. Architecture of the herpesvirus genomepackaging complex and implications for DNA translocation[J]. Protein Cell, 2020, 11(5): 339-351.
[6]	Rui Fu, Dawei Yu, Jilong Ren, Chongyang Li, Jing Wang, Guihai Feng, Xuepeng Wang, Haifeng Wan, Tianda Li, Libin Wang, Ying Zhang, Tang Hai, Wei Li, Qi Zhou. Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs[J]. Protein Cell, 2020, 11(2): 97-107.
[7]	Yingfeng Zheng, Xiuxing Liu, Wenqing Le, Lihui Xie, He Li, Wen Wen, Si Wang, Shuai Ma, Zhaohao Huang, Jinguo Ye, Wen Shi, Yanxia Ye, Zunpeng Liu, Moshi Song, Weiqi Zhang, Jing-Dong J. Han, Juan Carlos Izpisua Belmonte, Chuanle Xiao, Jing Qu, Hongyang Wang, Guang-Hui Liu, Wenru Su. A human circulating immune cell landscape in aging and COVID-19[J]. Protein Cell, 2020, 11(10): 740-770.
[8]	Hua Qin, Andong Zhao. Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics[J]. Protein Cell, 2020, 11(10): 707-722.
[9]	Xuemei Fu, Shouhai Wu, Bo Li, Yang Xu, Jingfeng Liu. Functions of p53 in pluripotent stem cells[J]. Protein Cell, 2020, 11(1): 71-78.
[10]	Feng Li, Yuanlong Ge, Dan Liu, Zhou Songyang. The role of telomere-binding modulators in pluripotent stem cells[J]. Protein Cell, 2020, 11(1): 60-70.
[11]	Hui Cheng, Zhaofeng Zheng, Tao Cheng. New paradigms on hematopoietic stem cell differentiation[J]. Protein Cell, 2020, 11(1): 34-44.
[12]	Si Wang, Zheying Min, Qianzhao Ji, Lingling Geng, Yao Su, Zunpeng Liu, Huifang Hu, Lixia Wang, Weiqi Zhang, Keiichiro Suzuiki, Yu Huang, Puyao Zhang, Tie-Shan Tang, Jing Qu, Yang Yu, Guang-Hui Liu, Jie Qiao. Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction[J]. Protein Cell, 2020, 11(1): 1-22.
[13]	Lili Yu, Kai-yuan Ji, Jian Zhang, Yanxia Xu, Yue Ying, Taoyi Mai, Shuxiang Xu, Qian-bing Zhang, Kai-tai Yao, Yang Xu. Core pluripotency factors promote glycolysis of human embryonic stem cells by activating GLUT1 enhancer[J]. Protein Cell, 2019, 10(9): 668-680.
[14]	Xing Zhang, Zunpeng Liu, Xiaoqian Liu, Si Wang, Yiyuan Zhang, Xiaojuan He, Shuhui Sun, Shuai Ma, Ng Shyh-Chang, Feng Liu, Qiang Wang, Xiaoqun Wang, Lin Liu, Weiqi Zhang, Moshi Song, Guang-Hui Liu, Jing Qu. Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis[J]. Protein Cell, 2019, 10(9): 649-667.
[15]	Nan Zhou, Kaili Liu, Yue Sun, Ying Cao, Jing Yang. Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition[J]. Protein Cell, 2019, 10(2): 87-103.

Viewed

Full text

Abstract

Cited

Shared

Discussed