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cellular reprogramming in farm animals： an overview of iPSC generation in the mammalian farm animal species

Journal of Animal Science and Biotechnology 2016年第4期7卷 459-467页

作者： J. Ogorevc S. Orehek P. DovcC Department of Animal Science Biotechnical Faculty University of LjubljanaDomzale Slovenia

Establishment of embryonic stem cell （ESC） lines has been successful in mouse and human, but not in farm animals. Development of direct reprogramming technology offers an alternative approach for generation of pluripotent stem cells, applicable also in farm animals. Induced pluripotent stem cells （iPSCs） represent practically limitless, ethically acceptable, individuum-specific source of pluripotent cells that can be generated from different types of somatic cells, iPSCs can differentiate to all cell types of an organism＇s body and have a tremendous potential for numerous applications in medicine, agriculture, and biotechnology. However, molecular mechanisms behind the reprogramming process remain largely unknown and hamper generation of bona fide iPSCs and their use in human clinical practice. Large animal models are essential to expand the knowledge obtained on rodents and facilitate development and validation of transplantation therapies in preclinical studies. Additionally, transgenic animals with special traits could be generated from genetically modified pluripotent cells, using advanced reproduction techniques. Despite their applicative potential, it seems that iPSCs in farm animals haven＇t received the deserved attention. The aim of this review was to provide a systematic overview on iPSC generation in the most important mammalian farm animal species （cattle, pig, horse, sheep, goat, and rabbit）, compare protein sequence similarity of pluripotency-related transcription factors in different species, and discuss potential uses of farm animal iPSCs. Literature mining revealed 32 studies, describing iPSC generation in pig （13 studies）, cattle （5） horse （5）, sheep （4）, goat （3）, and rabbit （2） that are summarized in a concise, tabular format.

关键词： cellular reprogramming Farm animals Induced pluripotent stem cells Pluripotency

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Potential of transposon-mediated cellular reprogramming towards cell-based therapies

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World Journal of Stem Cells 2020年第7期12卷 527-544页

作者： Dharmendra Kumar Taruna Anand Thirumala R Talluri Wilfried A Kues Animal Physiology and Reproduction Division ICAR-Central Institute for Research on BuffaloesHisar 125001India NCVTC ICAR-National Research Centre on EquinesHisar 125001India Equine Production Campus ICAR-National Research Centre on EquinesBikaner 334001India Friedrich-Loeffler-Institut Institute of Farm Animal GeneticsDepartment of BiotechnologyMariensee 31535Germany

Induced pluripotent stem(iPS)cells present a seminal discovery in cell biology and promise to support innovative treatments of so far incurable *** translate iPS technology into clinical trials,the safety and stability of these reprogrammed cells needs to be *** recent years,different non-viral transposon systems have been developed for the induction of cellular pluripotency,and for the directed differentiation into desired cell *** this review,we summarize the current state of the art of different transposon systems in iPS-based cell therapies.

关键词： Transposons Induced pluripotent stem cells Clinical applications cellular reprogramming Cell-based therapy Genetic correction

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Role of cellular reprogramming and epigenetic dysregulation in acquired chemoresistance in breast cancer

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Cancer Drug Resistance 2019年第2期2卷 297-312页

作者： Logeswari Ponnusamy Prathap Kumar S.Mahalingaiah Yu-Wei Chang Kamaleshwar P.Singh Department of Environmental Toxicology The Institute of Environmental and Human Health(TIEHH)Texas Tech UniversityLubbockTexas 79409USA Metabolism and Safety ZoetisKalamazooMichigan 49007USA Preclinical Safety AbbVieNorth ChicagoIllinois 60085USA

Acquired resistance to chemotherapy is a major limitation in clinical treatment for breast *** evidence from in vitro,in vivo and clinical studies suggest that acquired chemoresistance is progressive,multifactorial and involve genetic and epigenetic *** various mechanisms that contribute to chemoresistance,cellular reprogramming has extensively been implicated in breast cancer resistance *** reprogramming events such as acquisition of epithelial to mesenchymal transition(EMT)and cancer stemness(CSCs)not only provide cancer cells with reversible phenotypic plasticity and survival advantage against cytotoxicity but also leads to aggressiveness,metastasis,clinical resistance,tumor recurrence and poor *** transient and reversible nature of cellular reprogramming processes and their controlled interaction with epigenetic regulatory complexes strongly support the involvement of dynamic epigenetic regulatory network in governing the cellular reprogramming and associated acquired ***,epigenetic modulations are also gaining interest as promising interventions addressing the cancer cell reprogramming machinery to overcome acquired *** review discusses the previous reports and our recent findings that lead to current understanding of epigenetic dysregulation dictating the cellular reprogramming processes such as acquisition of EMT and CSCs phenotype and how they co-ordinate to establish acquired drug resistance in breast cancer.

关键词： Chemoresistance cellular reprogramming DNA methylation histone modifications breast cancer epithelial to mesenchymal transition cancer stem cell

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reprogramming cells with synthetic proteins

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Asian Journal of Andrology 2015年第3期17卷 394-402页

作者： Xiaoxiao Yang Vikas Malik Ralf Jauch Genome Regulation Laboratory Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences 190 Kai Yuan Avenue Science Park Guangzhou China

Conversion of one cell type into another cell type by forcibly expressing specific cocktails of transcription factors （TFs） has demonstrated that cell fates are not fixed and that cellular differentiation can be a two-way street with many intersections. These experiments also illustrated the sweeping potential of TFs to ＂read＂ genetically hardwired regulatory information even in cells where they are not normally expressed and to access and open up tightly packed chromatin to execute gene expression programs. cellular reprogramming enables the modeling of diseases in a dish, to test the efficacy and toxicity of drugs in patient-derived cells and ultimately, could enable cell-based therapies to cure degenerative diseases. Yet, producing terminally differentiated cells that fully resemble their in vivo counterparts in sufficient quantities is still an unmet clinical need. While efforts are being made to reprogram cells nongeneticaUy by using *** molecules, defined TF cocktails still dominate reprogramming protocols. Therefore; the optimization of TFs by protein engineering has emerged as a strategy to enhance reprogramming to produce functional, stable and safe cells for regenerative biomedicine. Engineering approaches focused on Oct4, MyoD, Sox17, Nanog and Mef2c and range from chimeric TFs with added transactivation domains, designer transcription activator-like effectors to activate endogenous TFs to reprogramming TFs with rationally engineered DNA recognition principles. Possibly, applying the complete toolkit of protein design to cellular reprogramming can help to remove the hurdles that, thus far, impeded the clinical use of cells derived from reprogramming technologies.

关键词： cellular reprogramming protein design protein engineering synthetic transcription factors transactivation

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Perspectives of pluripotent stem cells in livestock

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World Journal of Stem Cells 2021年第1期13卷 1-29页

作者： Dharmendra Kumar Thirumala R Talluri Naresh L Selokar Iqbal Hyder Wilfried A Ku Animal Physiology and Reproduction Division ICARCentral Institute for Research on BuffaloesHisar 125001India Equine Production Campus ICAR-National Research Centre on EquinesBikaner 334001India Department of Physiology NTR College of Veterinary ScienceGannavaram 521102India Department of Biotechnology Friedrich-Loeffler-InstituteFederal Institute of Animal HealthNeustadt 31535Germany

The recent progress in derivation of pluripotent stem cells(PSCs)from farm animals opens new approaches not only for reproduction,genetic engineering,treatment and conservation of these species,but also for screening novel drugs for their efficacy and toxicity,and modelling of human *** attempts to derive PSCs from the inner cell mass of blastocyst stages in farm animals were largely unsuccessful as either the cells survived for only a few passages,or lost their cellular potency;indicating that the protocols which allowed the derivation of murine or human embryonic stem(ES)cells were not sufficient to support the maintenance of ES cells from farm *** scenario changed by the innovation of induced pluripotency and by the development of the 3 inhibitor culture conditions to support naïve pluripotency in ES cells from livestock ***,the long-term culture of livestock PSCs while maintaining the full pluripotency is still challenging,and requires further ***,we review the current achievements in the derivation of PSCs from farm animals,and discuss the potential application areas.

关键词： Livestock cellular reprogramming Chimera Cell-therapy Ontogenesis Pluripotency

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Chemical-only reprogramming to pluripotency

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Frontiers in Biology 2016年第2期11卷 75-84页

作者： Behnam Ebrahimi Yazd Cardiovascular Research Center Shahid Sadoughi University of Medical Sciences Yazd Iran

Direct reprogramming technology has emerged as an outstanding technique for the generation of induced pluripotent stem cells （iPSCs） and various specialized cells directly from somatic ceils of different species. reprogramming techniques conventionally use viral vectors encoding transcription factors to induce fate conversion. However, the introduction of transgenes limits the therapeutic applications of the reprogrammed cells. To overcome safety-related concerns, small molecules offer some advantages over the existing methods for the control of gene expression and induction of cell fate conversion. Technical advances in optimizing concentrations, durations, structures, and combinations of small molecules make chemical reprogramming a safe and feasible method. This review provides a concise overview of cutting-edge findings regarding chemical-only reprogramming as one of the integration-free approaches to iPSC generation.

关键词： cellular reprogramming small molecule chemical reprogramming induced pluripotency regenerative medicine

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reprogramming barriers and enhancers:strategies to enhance the efficiency and kinetics of induced pluripotency

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Cell Regeneration 2015年第1期4卷 94-105页

作者： Behnam Ebrahimi Yazd Cardiovascular Research Center Shahid Sadoughi University of Medical SciencesYazdIran

Induced pluripotent stem cells are powerful tools for disease modeling,drug screening,and cell transplantation *** cells can be generated directly from somatic cells by ectopic expression of defined factors through a reprogramming ***,pluripotent reprogramming is an inefficient process because of various defined and unidentified *** studies dissecting the molecular mechanisms of reprogramming have methodically improved the quality,ease,and efficiency of *** strategies have been applied for enhancing reprogramming efficiency,including depletion/inhibition of barriers(p53,p21,p57,p16Ink4a/p19Arf,Mbd3,etc.),overexpression of enhancing genes(e.g.,FOXH1,C/EBP alpha,UTF1,and GLIS1),and administration of certain cytokines and small *** current review provides an in-depth overview of the cutting-edge findings regarding distinct barriers of reprogramming to pluripotency and strategies to enhance reprogramming *** incorporating the mechanistic insights from these recent findings,a combined method of inhibition of roadblocks and application of enhancing factors may yield the most reliable and effective approach in pluripotent reprogramming.

关键词： cellular reprogramming iPSCs Mbd3 C/EBPα p53

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