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| 1 | Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration显示文摘Accumulating evidence indicates an association between the circadian clock and the aging process.However,it remains elusive whether the deregulation of circadian clock proteins underlies stem cell aging and whether they are targetable for the alleviation of aging-associated syndromes.Here,we identified a transcription factor-independent role of CLOCK,a core component of the molecular circadian clock machinery,in counteracting human mesenchymal stem cell(hMSC)decay.CLOCK expression was decreased during hMSC aging.In addition,CLOCK deficiency accelerated hMSC senescence,whereas the overexpression of CLOCK,even as a transcriptionally inactive form,rejuvenated physiologically and pathologically aged hMSCs.Mechanistic studies revealed that CLOCK formed complexes with nuclear lamina proteins and KAP1,thus maintaining heterochromatin architecture and stabilizing repetitive genomic sequences.Finally,gene therapy with lentiviral vectors encoding CLOCK promoted cartilage regeneration and attenuated age-related articular degeneration in mice.These findings demonstrate a noncanonical role of CLOCK in stabilizing heterochromatin,promoting tissue regeneration,and mitigating aging-associated chronic diseases. | Chuqian Liang Zunpeng Liu Moshi Song Wei Li Zeming Wu Zehua Wang Qiaoran Wang Si Wang Kaowen Yan Liang Sun Tomoaki Hishida Yanning Cai Juan Carlos lzpisua Belmonte Pedro Guillen Piu Chan Qi Zhou Weiqi Zhang Jing Qu Guang-Hui Liu | 2021 | Cell Research2021，31，2： | 8 |
| 2 | Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction显示文摘In vivo genome editing represents a powerful strategy for both understanding basic biology and treating inherited diseases.However,it remains a challenge to develop universal and efficient in vivo genome-editing tools for tissues that comprise diverse cell types in either a dividing or non-dividing state.Here,we describe a versatile in vivo gene knock-in methodology that enables the targeting of a broad range of mutations and cell types through the insertion of a minigene at an intron of the target gene locus using an intracellularly linearized single homology arm donor.As a proof-of-concept,we focused on a mouse model of prematureaging caused by a dominant point mutation,which is difficult to repair using existing in vivo genome-editing tools.Systemic treatment using our new method ameliorated aging-associated phenotypes and extended animal lifespan,thus highlighting the potential of this methodology for a broad range of in vivo genome-editing applications. | Keiichiro Suzuki Mako Yamamoto Reyna Hernandez-Benitez Zhe Li Christopher Wei Rupa Devi Soligalla Emi Aizawa Fumiyuki Hatanaka Masakazu Kurita Pradeep Reddy Alejandro Ocampo Tomoaki Hishida Masahiro Sakurai Amy NNemeth Estrella Nunez Delicado Josep MCampistol Pierre Magistretti Pedro Guillen Concepcion Rodriguez Esteban Jianhui Gong Yilin Yuan Ying Gu Guang-Hui Liu Carlos Lopez-Otin Jun Wu Kun Zhang Juan Carlos Izpisua Belmonte | 2019 | Cell Research2019，29，10： | 2 |
| 3 | Interaction of a peptide corresponding to the loop domain of the S2 SARS-CoV virus protein with model membranes 显示文摘 | Guillen J de Ahneida RF Prieto M | 2009 | Mol Membr Biol2009，26，4： | 1 |
| 4 | Inversion of surface nuclear magnetic resonance data by an adapted monte carlo method applied to water resource characterization 显示文摘 | Guillen A Legchenko A | 2002 | Journal of Applied Geophysics2002，50，12： | 1 |
| 5 | Textural and physicochemical changes in salmon (Salmo salar) treated with commercial liquid smoke flavoudngs显示文摘 | MARTINEZ O SALMERON L GUILLEN M D | 2007 | Food Chemistry2007，100，2： | 1 |
| 6 | Textural and physicochemical changes in salmon (Salmo salar) treated with commercial liquid smoke flavourings显示文摘 | Martinez O Salmeron J Guillen M D | 2007 | Food Chemistry2007，100，2： | 1 |
| 7 | A comparative ultrastructural study of chondrosarcoma chordoid sarcoma and chordoma显示文摘 | Pardo-Mindan FJ Guillen FJ Villas C | 1981 | Cancer1981，47，11： | 1 |
| 8 | A Holistic Framework for Short Term Supply Chain Management Integrating Production and Corporate Financial Planning 显示文摘 | Gonzalo Guillen Mariana Badell | 2006 | Production Econo- mies2006，，6： | 1 |
| 9 | Restraint use, restraint orders, and the risk of falls in hospitalized patients显示文摘 | Shorr RI Guillen MK Rosenblatt LC | 2002 | J Am Geriatr Soc2002，50，： | 1 |
| 10 | Preparation and charac- terization of membranes formed by nonsolvent induced phase separation: A review显示文摘 | Guillen G R Pan Y Li M | 2011 | Ind Eng Chem Res2011，50，7： | 1 |
| 11 | Expression of CXCR6 and its ligand CXCL 16 in the lung in health and disease显示文摘 | Morgan AJ Guillen C Symon FA | 2005 | Clineal Experimental Allergy2005，35，12： | 1 |
| 12 | Polycyclic aromatic compounds: Extraction and determination in food显示文摘 | Maria D. Guillen | 1994 | Food Additives & Contaminants: Part A1994，，6： | 1 |
| 13 | Reduction of pomegranate chilling injury during storage after heat treatment: Role of polyamines显示文摘 | MIRDEHGHAN S H RAHEMIC M MARTINEZ-ROMERO D GUILLEN F VALVERDE J M ZAPATA P J SERRANO M VALERO D | 2007 | Postharvest Biology and Technology2007，44，： | 1 |
| 14 | Effects of exogenous putrescine on improving shelf life of four plum cultivars显示文摘 | SERRANO M MARTINEZ-ROMERO D GUILLEN F | 2003 | Postharvest Biology and Technology2003，30，： | 1 |
| 15 | Cytokine signaling during myocardial infarction: sequential appearance of IL-1βand IL-6显示文摘 | Guillen I Marino B Maris-jose G | 1995 | Am J Physiol1995，269，38： | 1 |
| 16 | Modification of the number and phenotype of stfiatal dopaminergic cells by carotid body graft 显示文摘 | San Sebastian W Guillen J Manfigue M | 2007 | Brain2007，130，5： | 1 |
| 17 | Efficacy of 1-MCP Treatment in Tomato Fruit显示文摘 | GUILLEN F CASTILLO S ZAPATA P J | 2007 | Postharvest Biology and Technology2007，43，： | 1 |
| 18 | Influence of oxygen in the deposition and annealing atmosphere on the characteristics of ITO thin films prepared by sputtering at room temperature 显示文摘 | Guillen C Herrero J | 2006 | Vacuum2006，80，6： | 1 |
| 19 | Cross-reactivity between Platanus pollen and vegetables显示文摘 | Caravaca F Guillen F et al | 2002 | AUergy2002，57，： | 1 |
| 20 | Cytokine signaling during myocardial infarction: sequential appearance of IL-113and IL-6 显示文摘 | Guillen I Marino B Maris-jose G | 1995 | Am J Physiol1995，269，： | 1 |
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