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Find and replace: editing human genome in pluripotent stem cells

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Protein & Cell 2011年第12期2卷 950-956页

作者： Huize Pan Weiqi zhang weizhou zhang Guang-Hui Liu National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Laboratory of Gene Regulation and Signal Transduction Department of PharmacologySchool of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA

Genetic manipulation of human pluripotent stem cells(hPSCs)provides a powerful tool for modeling diseases and developing future *** a number of independent genome-editing techniques were developed,including plasmid,bacterial artificial chromosome,adeno-associated virus vector,zinc finger nuclease,transcription activator-like effecter nuclease,and helper-dependent adenoviral *** editing has been successfully employed in different aspects of stem cell research such as gene correction,mutation knock-in,and establishment of reporter cell lines(Raya et al.,2009;Howden et al.,2011;Li et al.,2011;Liu et al.,2011b;Papapetrou et al.,2011;Sebastiano et al.,2011;Soldner et al.,2011;Zou et al.,2011a).These techniques combined with the utility of hPSCs will significantly influence the area of regenerative medicine.

关键词： gene targeting gene editing gene correction pluripotent stem cell

ROR1, an embryonic protein with an emerging role in cancer biology

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Protein & Cell 2014年第7期5卷 496-502页

作者： Nicholas Borcherding David Kusner Guang-Hui Liu weizhou zhang Department of Pathology College of Medicine University of Iowa Iowa City IA 52242 USA Department of Molecular and Cellular Biology College of Medicine University of Iowa Iowa City IA 52242 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorders Brain Tumor Center. Beiiina 100101. China

Receptor tyrosine kinase-Uke orphan receptor 1 （ROR1） is a member of the ROR family consisting of ROR1 and ROR2. RORs contain two distinct extracellular cysteinerich domains and one transmembrane domain. Within the intracellular portion, ROR1 possesses a tyrosine kinase domain, two serine/threonine-rich domains and a proline-rich domain. RORs have been studied in the context of embryonic patterning and neurogenesis through a variety of homologs. These physiologic functions are dichotomous based on the requirement of the kinase domain. A growing literature has established ROR1 as a marker for cancer, such as in CLL and other blood malignancies. In addition, ROR1 is critically involved in progression of a number of blood and solid malignancies. RORt has been shown to inhibit apoptosis, potentiate EGFR signaling, and induce epithelialmesenchymal transition （EMT）. Importantly, ROR1 is only detectable in embryonic tissue and generally absent in adult tissue, making the protein an ideal drug target for cancer therapy.

关键词： ROR1 embryogenesis cancer,immunotherapy

Non-viral iPSCs:a safe way for therapy?

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Protein & Cell 2012年第4期3卷 241-245页

作者： Weiqi zhang Di Guan Jing Qu weizhou zhang Guang-Hui Liu National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Laboratory of Gene Regulation and Signal Transduction Department of PharmacologySchool of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA

Patients-derived induced pluripotent stem cells(iPSCs)pro-vide an invaluable tool to study mechanisms of human dis-eases and also a limitless cellular source for clinical trans-plantation(Takahashi et al.,2007;Yu et al.,2007;Liu et al.,2011a,2011b;zhang et al.,2012).Retrovirus-or lenti-virus-based delivery systems have been serving as main-stream methods to generate patients-derived ***-ever,genomic integrations of reprogramming factors in virally generated iPSCs not only cause insertional mutagenesis but also lead to residual expression of reprogramming factors in iPSCs and their derivatives.

关键词： al. clinical programming

Converted neural cells: induced to a cure?

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Protein & Cell 2012年第2期3卷 91-97页

作者： Weiqi zhang Shunlei Duan Ying Li Xiuling Xu Jing Qu weizhou zhang Guang-Hui Liu National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Laboratory of Gene Regulation and Signal Transduction Department of PharmacologySchool of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA

Many neurodegenerative disorders such as Parkinson’s disease(PD),amyotrophic lateral sclerosis(ALS)and others often occur as a result of progressive loss of structure or function of ***,many groups were able to generate neural cells,either differentiated from induced pluripotent stem cells(iPSCs)or converted from somatic *** in converted neural cells have opened a new era to ease applications for modeling diseases and screening *** addition,the converted neural cells also hold the promise for cell replacement therapy(Kikuchi et al.,2011;Krencik et al.,2011;Kriks et al.,2011;Nori et al.,2011;Rhee et al.,2011;Schwartz et al.,2012).Here we will mainly discuss most recent progress on using converted functional neural cells to treat neurological diseases and highlight potential clinical challenges and future perspectives.

关键词： converted neural cell pluripotent stem cell transdifferentiation transplantation neurodegenerative diseases

nflammasomes in cancer： a double-edgecl sword

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Protein & Cell 2014年第1期5卷 12-20页

作者： Ryan Kolb Guang-Hui Liu Ann M. Janowski Fayyaz S. Sutterwala weizhou zhang Department of Pathology Carver College of Medicine University of Iowa Iowa City IA 52242 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Graduate Program in Immunology Carver College Of Medicine University of Iowa iowa City IA 52242 USA Department of Internal Medicine Carver College of Medicine University of Iowa Iowa City IA 52242 USA Veterans Affairs Medical Center Iowa City IA 52241 USA

Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent induc- ers of interleukin （IL）-I~ and IL-18 during infammation, are large protein complexes typically consisting of a Nod-like receptor （NLR）, the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific con- text. Here we summarize the role of different inflamma- some complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro- inflammatory cytokines play in immunity.

关键词： inflammasome cancer inflammation

DNA methylome:Unveiling your biological age

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Protein & Cell 2013年第10期4卷 723-725页

作者： Ming Li Wensu Liu Tingting Yuan Ruijun Bai Guang-Hui Liu weizhou zhang Jing Qu National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Be ijing Institute for Brain Disorders Beijing 100069China Department of Pathology Carver College of MedicineUniversity of IowaIowa CityIA 52242USA

Hannum and colleagues performed DNA methylation sequencing to examine the relationship between DNA methylome and aging ***,they succeeded in building a quantitative and reproducible model based on the epigenetic bio-markers to predict aging rate with high *** progress en-lightens us in many aspects particularly in applying this novel set of bio-markers on studying the mech-anism of aging rate using adult tissue-specifi c stem cells,building up a potential quantitative model to explore the mechanism for other epigenetic factors like non-coding RNA,and understanding the princi-ple and mechanism of 3D chromatin structure in epigenetic modulation.

关键词： aging applying mechanism

Photocatalytic ozonation-based degradation of phenol by ZnO—TiO_(2)nanocomposites in spinning disk reactor

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Chinese Journal of Chemical Engineering 2024年第8期72卷 74-84页

作者： Xueqing Ren Jiahao Niu Yan Li Lei Li Chao zhang Qiang Guo Qiaoling zhang weizhou Jiao Shanxi Province Key Laboratory of Higee-Oriented Chemical Engineering School of Chemistry and Chemical EngineeringNorth University of ChinaTaiyuan 030051China Shanxi Sanqiang New Energy Technology Co. LtdTaiyuan 030051China

Spinning disk reactor(SDR)has emerged as a novel process intensification photocatalytic reactor,and it has higher mass transfer efficiency and photon utilization for the degradation of toxic organic pollutants by advanced oxidation processes(AOPs).In this study,ZnO—TiO_(2)nanocomposites were prepared by solgel method,and coated on the disk of SDR by impregnation-pull-drying-calcination *** performance of catalyst was characterized by X-ray diffraction,scanning electron microscope,X-ray photoelectron spectroscopy,photoluminescence and ultraviolet—visible diffuse reflectance *** ozonation in SDR was used to remove phenol,and various factors on degradation effect were studied in *** results showed that the rate of degradation and mineralization reached 100%and 83.4%under UV light irradiation after 50 min,compared with photocatalysis and ozonation,the removal rate increased by 69.3%and 34.7%,and mineralization rate increased by 56.7%and 62.9%,which indicated that the coupling of photocatalysis and ozonation had a synergistic *** radical capture experiments demonstrated that the active species such as photogenerated holes(h^(+)),hydroxyl radicals(·OH),superoxide radical(·O_(2)-)were responsible for phenol degradation,and·OH played a leading role in the degradation process,while h+and·O_(2)^(-)played a non-leading role.

关键词： Spinning disk reactor Photocatalytic ozonation ZnO-TiO_(2)nanocomposites Advanced oxidation processes

Vitamin C alleviates aging defects in a stem cell model for Werner syndrome

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Protein & Cell 2016年第7期7卷 478-488页

作者： Ying Li weizhou zhang Liang Chang Yan Han Liang Sun Xiaojun Gong Hong Tang Zunpeng Liu Huichao Deng Yanxia Ye Yu Wang Jian Li Jie Qiao Jing Qu Weiqi zhang Guang-Hui Liu National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Department of Gynecology and Obstetrics Peking University Third Hospital Beijing 100191 China Department of Pathology Carver College Of Medicine University of lowa lowa City IA 52242 USA The Key Laboratory of Geriatrics Beijing Hospital & Beijing Institute of Geriatrics Ministry of Health Beijing 100730 China FSU-CAS Innovation Institute Foshan University Foshan 528000 China Beijing Institute for Brain Disorders Beijing 100069 China Department of Pediatrics Beijing Shijitan Hospital Capital Medical University Peking University Ninth School of Clinical Medicine Beijing 100038 China

Werner syndrome （WS） is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells （MSCs）. This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, teiomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN- deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS.

关键词： Vitamin C stem cell aging Wernersyndrome

Characterization of a novel mouse model with genetic deletion of CD177

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Protein & Cell 2015年第2期6卷 117-126页

作者： Qing Xie Julia Klesney-Tait Kathy Keck Corey Parlet Nicholas Borcherding Ryan Kolb Wei Li Lorraine Tygrett Thomas Waldschmidt Alicia Olivier Songhai Chen Guang-Hui Liu Guang-Hui Liu Xiangrui Li weizhou zhang College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China Department of Pathology Holden Comprehensive Cancer Center Carver College of Medicine/University of Iowa Iowa IA 52242 USA Department of Internal Medicine Carver College of Medicine/University of Iowa Iowa IA 52242 USA Department of Pharmacology Carver College of Medicine/University of Iowa Iowa IA 52242 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorders Beijing 100069 China

Neutrophils play an essential role in the innate immune response to infection. Neutrophils migrate from the vasculature into the tissue in response to infection. Recently, a neutrophil cell surface receptor, CD177, was shown to help mediate neutrophil migration across the endothelium through interactions with PECAMI. We examined a publicly available gene array dataset of CD177 expression from human neutrophils following pulmonary endotoxin instillation. Among all 22,214 genes examined, CD177 mRNA was the most upregu- lated following endotoxin exposure. The high level of CD177 expression is also maintained in airspace neu- trophils, suggesting a potential involvement of CD177 in neutrophil infiltration under infectious diseases. To determine the role of CD177 in neutrophils in vivo, we constructed a CD177-genetic knockout mouse model. The mice with homozygous deletion of CD177 have no discernible phenotype and no significant change in immune cells, other than decreased neutrophil counts in peripheral blood. We examined the role of CD177 in neutrophil accumulation using a skin infection model with Staphylococcus aureus. CD177 deletion reducedneutrophil counts in inflammatory skin caused by S. aureus. Mechanistically we found that CD177 deletion in mouse neutrophils has no significant impact in CXCLI/ KC- or fMLP-induced migration, but led to significant cell death. Herein we established a novel genetic mouse model to study the role of CD177 and found that CD177 plays an important role in neutrophils.

关键词： CD177 neutrophil mouse model geneticdeletion