|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Bone Morphogenetic Protein (BMP) signaling in development and human diseases显示文摘Bone Morphogenetic Proteins(BMPs)are a group of signaling molecules that belongs to the Transforming Growth Factor-b(TGF-b)superfamily of proteins.Initially discovered for their ability to induce bone formation,BMPs are now known to play crucial roles in all organ systems.BMPs are important in embryogenesis and development,and also in maintenance of adult tissue homeostasis.Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects,highlighting the essential functions of BMPs.In this review,we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development.A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling. | Richard N.Wang Jordan Green Zhongliang Wang Youlin Deng Min Qiao Michael Peabody Qian Zhang Jixing Ye Zhengjian Yan Sahitya Denduluri Olumuyiwa Idowu Melissa Li Christine Shen Alan Hu Rex C.Haydon Richard Kang James Mok Michael J.Lee Hue L.Luu Lewis L.Shi | 2014 | Genes & Diseases2014，1，1： | 47 |
| 2 | Mesenchymal stem cells: Molecular characteristics and clinical applications显示文摘Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells with the capacity to differentiate into tissues of both mesenchymal and non-mesenchymal origin. MSCs can differentiate into osteoblastic, chondrogenic, and adipogenic lineages, although recent studies have demonstrated that MSCs are also able to differentiate into other lineages, including neuronal and cardiomyogenic lineages. Since their original isolation from the bone marrow, MSCs have been successfully harvested from many other tissues. Their ease of isolation and ex vivo expansion combined with their immunoprivileged nature has made these cells popular candidates for stem cell therapies. These cells have the potential to alter disease pathophysiology through many modalities including cytokine secretion, capacity to differentiate along various lineages, immune modulation and direct cell-cell interaction with diseased tissue. Here we first review basic features of MSC biology including MSC characteristics in culture, homing mechanisms, differentiation capabilities and immune modulation. We then highlight some in vivo and clinical evidence supporting the therapeutic roles of MSCs and their uses in orthopedic, autoimmune, and ischemic disorders. | Farbod Rastegar Deana Shenaq Eric R Wagner Stephanie H Kim Russell R Reid Hue H Luu Rex C Haydon | 2010 | World Journal of Stem Cells2010，2，4： | 35 |
| 3 | Breast cancer development and progression:Risk factors,cancer stem cells,signaling pathways,genomics,and molecular pathogenesis显示文摘As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast.While the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this malignancy.Breast cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in between.Within the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites.It is important to distinguish between the various subtypes because they have different prognoses and treatment implications.As there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem cells.Normal breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell motility.Furthermore,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast cancer.This review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer. | Yixiao Feng Mia Spezia Shifeng Huang Chengfu Yuan Zongyue Zeng Linghuan Zhang Xiaojuan Ji Wei Liu Bo Huang Wenping Luo Bo Liu Yan Lei Scott Du Akhila Vuppalapati Hue H.Luu Rex C.Haydon Tong-Chuan He Guosheng Ren | 2018 | Genes & Diseases2018，5，2： | 24 |
| 4 | The versatile functions of Sox9 in development,stem cells,and human diseases显示文摘The transcription factor Sox9 was first discovered in patients with campomelic dysplasia,a haploinsufficiency disorder with skeletal deformities caused by dysregulation of Sox9 expression during chondrogenesis.Since then,its role as a cell fate determiner during embryonic development has been well characterized;Sox9 expression differentiates cells derived from all three germ layers into a large variety of specialized tissues and organs.However,recent data has shown that ectoderm-and endoderm-derived tissues continue to express Sox9 in mature organs and stem cell pools,suggesting its role in cell maintenance and specification during adult life.The versatility of Sox9 may be explained by a combination of posttranscriptional modifications,binding partners,and the tissue type in which it is expressed.Considering its importance during both development and adult life,it follows that dysregulation of Sox9 has been implicated in various congenital and acquired diseases,including fibrosis and cancer.This review provides a summary of the various roles of Sox9 in cell fate specification,stem cell biology,and related human diseases.Ultimately,understanding the mechanisms that regulate Sox9 will be crucial for developing effective therapies to treat disease caused by stem cell dysregulation or even reverse organ damage. | Alice Jo Sahitya Denduluri Bosi Zhang Zhongliang Wang Liangjun Yin Zhengjian Yan Richard Kang Lewis L.Shi James Mok Michael J.Lee Rex C.Haydon | 2014 | Genes & Diseases2014，1，2： | 16 |
| 5 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 6 | Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)显示文摘Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and myocytes.MSCs represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult tissues.At least 14 BMPs have been identified in mammals.Different BMPs exert distinct but overlapping biological functions.Through a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of MSCs.Nonetheless,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully elucidated.Here,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of BMPs.Hierarchical clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 cluster.We also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase pathway.Furthermore,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR pathways.While the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs. | Linghuan Zhang Qing Luo Yi Shu Zongyue Zeng Bo Huang Yixiao Feng Bo Zhang Xi Wang Yan Lei Zhenyu Ye Ling Zhao Daigui Cao Lijuan Yang Xian Chen Bin Liu William Wagstaff Russell R*Reid Hue H*Luu Rex C*Haydon Michael J*Lee Jennifer Moriatis Wolf Zhou Fu Tong-Chuan He Quan Kang | 2019 | Genes & Diseases2019，6，3： | 11 |
| 7 | Highly expressed BMP9/GDF2 in postnatal mouse liver and lungs may account for its pleiotropic effects on stem cell differentiation,angiogenesis,tumor growth and metabolism显示文摘Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis.However,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed.Here,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice.By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult placenta.We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages.We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older mice.Interestingly,Bmp9 was only expressed at low to modest levels in developing bones.BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs.Furthermore,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues.However,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic fashion.Thus,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood. | Wei Liu Zhongliang Deng Zongyue Zeng Jiaming Fan Yixiao Feng Xi Wang Daigui Cao Bo Zhang Lijuan Yang Bin Liu Mikhail Pakvasa William Wagstaff Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Huiming Ding Yongtao Zhang Changchun Niu Rex C.Haydon Hue H.Luu Jennifer Moriatis Wolf Michael J.Lee Wei Huang Tong-Chuan He Yulong Zou | 2020 | Genes & Diseases2020，7，2： | 9 |
| 8 | Multifaceted signaling regulators of chondrogenesis:Implications in cartilage regeneration and tissue engineering显示文摘Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature.Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue.Here,we review the current understanding of the most important biological regulators of chondrogenesis and their interactions,to provide insight into potential applications for cartilage tissue engineering.These include various signaling pathways,including fibroblast growth factors(FGFs),transforming growth factor b(TGF-b)/bone morphogenic proteins(BMPs),Wnt/b-catenin,Hedgehog,Notch,hypoxia,and angiogenic signaling pathways.Transcriptional and epigenetic regulation of chondrogenesis will also be discussed.Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering. | Jordan D.Green Viktor Tollemar Mark Dougherty Zhengjian Yan Liangjun Yin Jixing Ye Zachary Collier Maryam K.Mohammed Rex C.Haydon Hue H.Luu Richard Kang Michael J.Lee Sherwin H.Ho Tong-Chuan He Lewis L.Shi Aravind Athiviraham | 2015 | Genes & Diseases2015，2，4： | 9 |
| 9 | Guidelines for Colonoscopy Surveillance After Screening and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer显示文摘 | David A. Lieberman Douglas K. Rex Sidney J. Winawer Francis M. Giardiello David A. Johnson Theodore R. Levin | 2012 | Gastroenterology2012，，3： | 8 |
| 10 | Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference显示文摘Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics. | Shujuan Yan Ruyi Zhang Ke Wu Jing Cui Shifeng Huang Xiaojuan Ji Liping An Chengfu Yuan Cheng Gong Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Bo Liu Rex C.Haydon Michael J.Lee Russell R.Reid Jennifer Moriatis Wolf Qiong Shi Hue H.Luu Tong-Chuan He Yaguang Weng | 2018 | Genes & Diseases2018，5，2： | 8 |
| 11 | Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline From the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology显示文摘 | Bernard Levin David A. Lieberman Beth McFarland Kimberly S. Andrews Durado Brooks John Bond Chiranjeev Dash Francis M. Giardiello Seth Glick David Johnson C. Daniel Johnson Theodore R. Levin Perry J. Pickhardt Douglas K. Rex Robert A. Smith Alan Thorson S | 2008 | Gastroenterology2008，，5： | 8 |
| 12 | 灭鼠剂适口性衡量标准研究——维生素D_3和磷化锌的适口性比较显示文摘本文提出了一种新的评价灭鼠剂适口性的方法,即用直线回归方程来描述灭鼠剂的适口性,具体做法是以毒饵的摄食系数为纵座标(Y),以灭鼠剂在毒饵中的浓度的对数为横座标(X),求出直线回归方程。本法的优点是可以反映毒饵的适口性随灭鼠剂在毒饵中的浓度改变而产生变化的趋势,并以磷化锌和维生素D_3为实例加以说明。相关系数测定表明,磷化锌的摄食系数与其对数浓度之间存在着非常显著的负相关关系(r=-0.8923,p<0.001),其直线回归方程为Y=0.4153-0.2541x。实验结果表明,磷化锌的最低适用浓度和最适浓度均为2%,而维生素D_3的最低适用浓度为0.1%,最适浓度为0.2%。 | 李镜辉 Rex E.Marsh | 1990 | 兽类学报1990，10，2： | 7 |
| 13 | The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps显示文摘 | Douglas K. Rex Charles Kahi Michael O’Brien T.R. Levin Heiko Pohl Amit Rastogi Larry Burgart Tom Imperiale Uri Ladabaum Jonathan Cohen David A. Lieberman | 2011 | Gastrointestinal Endoscopy2011，，3： | 7 |
| 14 | 豌豆在肉鸡日粮中的应用效果研究显示文摘选取3 240只AA肉仔鸡随机分为6组,每组6个重复,每个重复90只鸡。对照组饲喂基础日粮,试验组分别在饲养的前、中、后期添加10%、20%、30%的豌豆来研究在肉鸡日粮中添加不同水平的豌豆对肉鸡生产性能的影响。结果表明:在试验前期,不管日粮中添加10%、20%、30%的豌豆,均可极显著(P<0.01)降低肉鸡的日采食量,但从肉鸡全程的饲养数据看,即使前、中、后期日粮中的豌豆添加比例均达到30%,对肉鸡全程的生产性能(成活率、末重和肥育指数)和全净膛率没有显著影响(P>0.05)。 | 吕明斌 乔玉锋 REX NEWKIRK | 2007 | 中国畜牧杂志2007，43，7： | 7 |
| 15 | Standard forward-viewing colonoscopy versus full-spectrum endoscopy: an international, multicentre, randomised, tandem colonoscopy trial显示文摘 | Ian M Gralnek Peter D Siersema Zamir Halpern Ori Segol Alaa Melhem Alain Suissa Erwin Santo Alan Sloyer Jay Fenster Leon M G Moons Vincent K Dik Ralph B D’Agostino Douglas K Rex | 2014 | Lancet Oncology2014，，3： | 6 |
| 16 | Stem cell therapy for chronic skin wounds in the era of personalized medicine:From bench to bedside显示文摘With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care. | Elam Coalson Elliot Bishop Wei Liu Yixiao Feng Mia Spezia Bo Liu Yi Shen Di Wu Scott Du Alexander J.Li Zhenyu Ye Ling Zhao Daigui Cao Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Rex C.Haydon Lewis Shi Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He Russell R.Reid | 2019 | Genes & Diseases2019，6，4： | 6 |
| 17 | Ferroptosis as a novel form of regulated cell death:Implications in the pathogenesis,oncometabolism and treatment of human cancer显示文摘The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy.Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells.Anti-tumor drugs were developed to induce apoptosis,but some patient’s show apoptosis escape and chemotherapy resistance.Therefore,other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment.Ferroptosis is a newly discovered iron-dependent,non-apoptotic type of cell death that is highly negatively correlated with cancer development.Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis.This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment. | Feifei Pu Fengxia Chen Zhicai Zhang Deyao Shi Binlong Zhong Xiao Lv Andrew Blake Tucker Jiaming Fan Alexander J.Li Kevin Qin Daniel Hu Connie Chen Hao Wang Fang He Na Ni Linjuan Huang Qing Liu William Wagstaff Hue H.Luu Rex C.Haydon Le Shen Tong-Chuan He Jianxiang Liu Zengwu Shao | 2022 | Genes & Diseases2022，9，2： | 6 |
| 18 | Implementation of an in-house flow cytometric analysis of DNA fragmentation in spermatozoa显示文摘An increased amount of DNA fragme ntation in the spermatozoa(SDF)is linked to male in fertility.The Sperm Chromati n Structure Assay(SCSA)is widely used for analysis of SDF.However,the current software(SCSASoftR)linked to this assay is licensed and often located within larger diagnostic centers.In this study,we present a protocol for using other types of software than SCSASoftR to determine the SDF index(DFI)with clinical relevance.This protocol is engineered after collect!ng and analyzing 254 samples from fertility patients and sperm donors over a 15-month period.DFI is analyzed using a strict protocol where the spermatozoa are treated with a strong acid(pH 1.2)followed by acridine orange.DFI is determined by a standard flow cytometric software,FACSDiva 6.1.3.Analysis of the outcome of the fertility treatment is included for 137 patients receiving either intrauterine inseminations(IUI)or timed coitus(TC).The results show that the chance of pregnancy decli nes as DFI in creases.We also found that the male DFI affects the chanee of pregnancy independent of the female age.We have shown that a standard flow cytometric software can be used when determi ning a clinical releva nt DFI.These findings are a sign ificant step toward impleme nting the an alysis as a part of the routi ne,in・house diag no sing of the male fertility patient and subseque ntly optimizing the treatme nt course of the couple with reduced human and financial costs. | Anne Sofie Rex Chunsen Wu Jorn Aagaard Jens Fedder | 2020 | Asian Journal of Andrology2020，22，3： | 5 |
| 19 | Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes(imPODs)显示文摘Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney.Maintaining the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell biology.As mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPC)was established from the Immortomouse over 20 years ago.However,the utility of the tsPC cells is hampered by the practical inconvenience of culturing these cells.In this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT sites.We show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP recombinase.The imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker Synaptopodin.The imPOD cells do not form tumor-like masses in vivo.We further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors CTGF and Col1a1.Collectively,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions. | Xinyi Yu Liqun Chen Ke Wu Shujuan Yan Ruyi Zhang Chen Zhao Zongyue Zeng Yi Shu Shifeng Huang Jiayan Lei Xiaojuan Ji Chengfu Yuan Linghuan Zhang Yixiao Feng Wei Liu Bo Huang Bo Zhang Wenping Luo Xi Wang Bo Liu Rex C.Haydon Hue H.Luu Tong-Chuan He Hua Gan | 2018 | Genes & Diseases2018，5，2： | 5 |
| 20 | Sustained high level transgene expression in mammalian cells mediated by the optimized piggyBac transposon system显示文摘Sustained,high level transgene expression in mammalian cells is desired in many cases for studying gene functions.Traditionally,stable transgene expression has been accomplished by using retroviral or lentiviral vectors.However,such viral vector-mediated transgene expression is often at low levels and can be reduced over time due to low copy numbers and/or chromatin remodeling repression.The piggyBac transposon has emerged as a promising nonviral vector system for efficient gene transfer into mammalian cells.Despite its inherent advantages over lentiviral and retroviral systems,piggyBac system has not been widely used,at least in part due to their limited manipulation flexibilities.Here,we seek to optimize piggyBac-mediated transgene expression and generate a more efficient,user-friendly piggyBac system.By engineering a panel of versatile piggyBac vectors and constructing recombinant adenoviruses expressing piggyBac transposase(PBase),we demonstrate that adenovirusmediated PBase expression significantly enhances the integration efficiency and expression level of transgenes in mesenchymal stem cells and osteosarcoma cells,compared to that obtained from co-transfection of the CMV-PBase plasmid.We further determine the drug selection timeline to achieve optimal stable transgene expression.Moreover,we demonstrate that the transgene copy number of piggyBac-mediated integration is approximately 10 times higher than that mediated by retroviral vectors.Using the engineered tandem expression vector,we show that three transgenes can be simultaneously expressed in a single vector with high efficiency.Thus,these results strongly suggest that the optimized piggyBac system is a valuable tool for making stable cell lines with sustained,high transgene expression. | Xiang Chen Jing Cui Zhengjian Yan Hongmei Zhang Xian Chen Ning Wang Palak Shah Fang Deng Chen Zhao Nisha Geng Melissa Li Sahitya K.Denduluri Rex C.Haydon Hue H.Luu Russell R.Reid Tong-Chuan He | 2015 | Genes & Diseases2015，2，1： | 5 |
您所在的机构暂未开通此部分的功能，请联系管理员