Cell Regeneration最新文献

{"title":"Pharmacological manipulation of transcription factor protein-protein interactions: opportunities and obstacles","authors":"Frank Fontaine ,&nbsp;Jeroen Overman ,&nbsp;Mathias François","doi":"10.1186/s13619-015-0015-x","DOIUrl":"10.1186/s13619-015-0015-x","url":null,"abstract":"<div><p>Much research on transcription factor biology and their genetic pathways has been undertaken over the last 30 years, especially in the field of developmental biology and cancer. Yet, very little is known about the molecular modalities of highly dynamic interactions between transcription factors, genomic DNA, and protein partners. Methodological breakthroughs such as RNA-seq (RNA-sequencing), ChIP-seq (chromatin immunoprecipitation sequencing), RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins), and single-molecule imaging will dramatically accelerate the discovery rate of their molecular mode of action in the next few years.</p><p>From a pharmacological viewpoint, conventional methods used to target transcription factor activity with molecules mimicking endogenous ligands fail to achieve high specificity and are limited by a lack of identification of new molecular targets. Protein-protein interactions are likely to represent one of the next major classes of therapeutic targets. Transcription factors, known to act mostly via protein-protein interaction, may well be at the forefront of this type of drug development. One hurdle in this field remains the difficulty to collate structural data into meaningful information for rational drug design. Another hurdle is the lack of chemical libraries meeting the structural requirements of protein-protein interaction disruption.</p><p>As more attempts at modulating transcription factor activity are undertaken, valuable knowledge will be accumulated on the modality of action required to modulate transcription and how these findings can be applied to developing transcription factor drugs. Key discoveries will spawn into new therapeutic approaches not only as anticancer targets but also for other indications, such as those with an inflammatory component including neurodegenerative disorders, diabetes, and chronic liver and kidney diseases.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:2"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0015-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33194627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell therapy for amyotrophic lateral sclerosis","authors":"Zhijuan Mao ,&nbsp;Suming Zhang ,&nbsp;Hong Chen","doi":"10.1186/s13619-015-0026-7","DOIUrl":"10.1186/s13619-015-0026-7","url":null,"abstract":"<div><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of motor neurons. Currently, no effective therapy is available to treat ALS, except for Riluzole, which has only limited clinical benefits. Stem-cell-based therapy has been intensively and extensively studied as a potential novel treatment strategy for ALS and has been shown to be effective, at least to some extent. In this article, we will review the current state of research on the use of stem cell therapy in the treatment of ALS and discuss the most promising stem cells for the treatment of ALS.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:11"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0026-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt/β-catenin signaling in heart regeneration","authors":"Gunes Ozhan ,&nbsp;Gilbert Weidinger","doi":"10.1186/s13619-015-0017-8","DOIUrl":"10.1186/s13619-015-0017-8","url":null,"abstract":"<div><p>The ability to repair damaged or lost tissues varies significantly among vertebrates. The regenerative ability of the heart is clinically very relevant, because adult teleost fish and amphibians can regenerate heart tissue, but we mammals cannot. Interestingly, heart regeneration is possible in neonatal mice, but this ability is lost within 7 days after birth. In zebrafish and neonatal mice, lost cardiomyocytes are regenerated via proliferation of spared, differentiated cardiomyocytes. While some cardiomyocyte turnover occurs in adult mammals, the cardiomyocyte production rate is too low in response to injury to regenerate the heart. Instead, mammalian hearts respond to injury by remodeling of spared tissue, which includes cardiomyocyte hypertrophy. Wnt/β-catenin signaling plays important roles during vertebrate heart development, and it is re-activated in response to cardiac injury. In this review, we discuss the known functions of this signaling pathway in injured hearts, its involvement in cardiac fibrosis and hypertrophy, and potential therapeutic approaches that might promote cardiac repair after injury by modifying Wnt/β-catenin signaling. Regulation of cardiac remodeling by this signaling pathway appears to vary depending on the injury model and the exact stages that have been studied. Thus, conflicting data have been published regarding a potential role of Wnt/β-catenin pathway in promotion of fibrosis and cardiomyocyte hypertrophy. In addition, the Wnt inhibitory secreted Frizzled-related proteins (sFrps) appear to have Wnt-dependent and Wnt-independent roles in the injured heart. Thus, while the exact functions of Wnt/β-catenin pathway activity in response to injury still need to be elucidated in the non-regenerating mammalian heart, but also in regenerating lower vertebrates, manipulation of the pathway is essential for creation of therapeutically useful cardiomyocytes from stem cells in culture. Hopefully, a detailed understanding of the <em>in vivo</em> role of Wnt/β-catenin signaling in injured mammalian and non-mammalian hearts will also contribute to the success of current efforts towards developing regenerative therapies.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:3"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0017-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34273967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay between metabolic homeostasis and neurodegeneration: insights into the neurometabolic nature of amyotrophic lateral sclerosis","authors":"S.T. Ngo ,&nbsp;F.J. Steyn","doi":"10.1186/s13619-015-0019-6","DOIUrl":"10.1186/s13619-015-0019-6","url":null,"abstract":"<div><p>Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease that is characterized by the selective degeneration of upper motor neurons and lower spinal motor neurons, resulting in the progressive paralysis of all voluntary muscles. Approximately 10 % of ALS cases are linked to known genetic mutations, with the remaining 90 % of cases being sporadic. While the primary pathology in ALS is the selective death of upper and lower motor neurons, numerous studies indicate that an imbalance in whole body and/or cellular metabolism influences the rate of progression of disease. This review summarizes current research surrounding the impact of impaired metabolic physiology in ALS. We extend ideas to consider prospects that lie ahead in terms of how metabolic alterations may impact the selective degeneration of neurons in ALS and how targeting of adenosine triphosphate-sensitive potassium (K_ATP) channels may represent a promising approach for obtaining neuroprotection in ALS.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:5"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0019-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33964096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo","authors":"Songwei He ,&nbsp;Yiping Guo ,&nbsp;Yixin Zhang ,&nbsp;Yuan Li ,&nbsp;Chengqian Feng ,&nbsp;Xiang Li ,&nbsp;Lilong Lin ,&nbsp;Lin Guo ,&nbsp;Haitao Wang ,&nbsp;Chunhua Liu ,&nbsp;Yi Zheng ,&nbsp;Chuanming Luo ,&nbsp;Qiang Liu ,&nbsp;Fuhui Wang ,&nbsp;Hao Sun ,&nbsp;Lining Liang ,&nbsp;Lingyu Li ,&nbsp;Huanxing Su ,&nbsp;Jiekai Chen ,&nbsp;Duanqing Pei ,&nbsp;Hui Zheng","doi":"10.1186/s13619-015-0027-6","DOIUrl":"10.1186/s13619-015-0027-6","url":null,"abstract":"<div><h3>Background</h3><p>Currently, direct conversion from somatic cells to neurons requires virus-mediated delivery of at least one transcriptional factor or a combination of several small-molecule compounds. Delivery of transcriptional factors may affect genome stability, while small-molecule compounds may require more evaluations when applied <em>in vivo</em>. Thus, a defined medium with only conventional growth factors or additives for cell culture is desirable for inducing neuronal trans-differentiation.</p></div><div><h3>Results</h3><p>Here, we report that a defined medium (5C) consisting of basic fibroblast growth factor (bFGF), N2 supplement, leukemia inhibitory factor, vitamin C (Vc), and β-mercaptoethanol (βMe) induces the direct conversion of somatic cells to cells with neuronal characteristics. Application of 5C medium converted mouse embryonic fibroblasts (MEFs) into TuJ+ neuronal-like cells, which were capable of survival after being transplanted into the mouse brain. The same 5C medium could convert primary rat astrocytes into neuronal-like cells with mature electrophysiology characteristics <em>in vitro</em> and facilitated the recovery of brain injury, possibly by inducing similar conversions, when infused into the mouse brain <em>in vivo</em>. Crucially, 5C medium could also induce neuronal characteristics in several human cell types.</p></div><div><h3>Conclusions</h3><p>In summary, this 5C medium not only provides a means to derive cells with neuronal characteristics without viral transfection <em>in vitro</em> but might also be useful to produce neurons <em>in vivo</em> for neurodegenerative disease treatment.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:12"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0027-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ETV2 expression increases the efficiency of primitive endothelial cell derivation from human embryonic stem cells","authors":"Anne G Lindgren ,&nbsp;Matthew B Veldman ,&nbsp;Shuo Lin","doi":"10.1186/s13619-014-0014-3","DOIUrl":"10.1186/s13619-014-0014-3","url":null,"abstract":"<div><h3>Background</h3><p>Endothelial cells line the luminal surface of blood vessels and form a barrier between the blood and other tissues of the body. Ets variant 2 (<em>ETV2</em>) is transiently expressed in both zebrafish and mice and is necessary and sufficient for vascular endothelial cell specification. Overexpression of this gene in early zebrafish and mouse embryos results in ectopic appearance of endothelial cells. Ectopic expression of <em>ETV2</em> in later development results in only a subset of cells responding to the signal.</p></div><div><h3>Findings</h3><p>We have examined the expression pattern of <em>ETV2</em> in differentiating human embryonic stem cells (ESCs) to determine when the peak of <em>ETV2</em> expression occurs. We show that overexpression of <em>ETV2</em> in differentiating human ESC is able to increase the number of endothelial cells generated when administered during or after the endogenous peak of gene expression.</p></div><div><h3>Conclusions</h3><p>Addition of exogenous <em>ETV2</em> to human ESCs significantly increased the number of cells expressing angioblast genes without arterial or venous specification. This may be a viable solution to generate <em>in vitro</em> endothelial cells for use in research and in the clinic.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:1"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-014-0014-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33137417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Oct4 in the early embryo development","authors":"Guangming Wu ,&nbsp;Hans R Schöler","doi":"10.1186/2045-9769-3-7","DOIUrl":"10.1186/2045-9769-3-7","url":null,"abstract":"<div><p>Oct4 is a key component of the pluripotency regulatory network, and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells (ESCs) or their differentiation into trophoblast. Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development. However, the genetic elimination of maternal <em>Oct4</em> using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4–depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect. These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency. This conclusion is further supported by the formation of <em>Oct4</em>-GFP– and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic <em>Oct4</em> expression and the reprogramming of fibroblasts into fully pluripotent cells by <em>Oct4</em>-deficient oocytes.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"3 1","pages":"Article 3:7"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-9769-3-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32824479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined influence of basal media and fibroblast growth factor on the expansion and differentiation capabilities of adipose-derived stem cells","authors":"Mark Ahearne ,&nbsp;Joanne Lysaght ,&nbsp;Amy P Lynch","doi":"10.1186/2045-9769-3-13","DOIUrl":"10.1186/2045-9769-3-13","url":null,"abstract":"<div><h3>Background</h3><p>Interest in adipose-derived stem cells (ASCs) has increased in recent years due to their multi-linage differentiation capabilities. While much work has been done to optimize the differentiation media, few studies have focused on examining the influence of different expansion media on cell behavior. In this study, three basal media (low glucose Dulbecco’s modified Eagle’s medium (DMEM), high glucose DMEM and DMEM-F12) supplemented with or without fibroblast growth factor 2 (FGF) were examined to assess their suitability for expanding ASCs.</p></div><div><h3>Findings</h3><p>Flow cytometry, colony-forming unit assays (CFU-Fs) and differentiation assays were utilized to study cell behavior. High glucose media CFU-Fs produced fewest colonies while the addition of FGF increased colony size. By passage 2, the majority of cells were positive for CD44, 45, 73, 90 and 105 and negative for CD14, 31 and 45, indicating a mesenchymal phenotype. A sub-population of CD34 positive cells was present among passage 2 cells; however, by passage 4 the cells were negative for CD34. FGF has a negative effective on passage 4 ASC adipogenesis and high glucose media plus FGF-enhanced osteogenic capacity of passage 4 ASCs. FGF supplemented basal media were most suitable for chondrogenesis. High glucose media plus FGF appeared to be the most beneficial for priming ASCs to induce a keratocyte phenotype.</p></div><div><h3>Conclusions</h3><p>These findings demonstrate the reciprocal effect FGF and basal media have on ASCs. This research has implications for those interested regenerating bone, cartilage, cornea or adipose tissues.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"3 1","pages":"Article 3:13"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-9769-3-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33145248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of knockout rabbits using transcription activator-like effector nucleases","authors":"Yu Wang ,&nbsp;Nana Fan ,&nbsp;Jun Song ,&nbsp;Juan Zhong ,&nbsp;Xiaogang Guo ,&nbsp;Weihua Tian ,&nbsp;Quanjun Zhang ,&nbsp;Fenggong Cui ,&nbsp;Li Li ,&nbsp;Philip N Newsome ,&nbsp;Jon Frampton ,&nbsp;Miguel A Esteban ,&nbsp;Liangxue Lai","doi":"10.1186/2045-9769-3-3","DOIUrl":"10.1186/2045-9769-3-3","url":null,"abstract":"<div><p>Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platforms contributing to redefine the boundaries of modern biological research. They are composed of a non-specific cleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications by inducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases have been employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, respectively. This approach is cost effective, relatively quick, and can produce invaluable models for human disease studies, biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbits using transcription activator-like effector nucleases, and a perspective of the field.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"3 1","pages":"Article 3:3"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-9769-3-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32824474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"glbase: a framework for combining, analyzing and displaying heterogeneous genomic and high-throughput sequencing data","authors":"Andrew Paul Hutchins ,&nbsp;Ralf Jauch ,&nbsp;Mateusz Dyla ,&nbsp;Diego Miranda-Saavedra","doi":"10.1186/2045-9769-3-1","DOIUrl":"10.1186/2045-9769-3-1","url":null,"abstract":"<div><p>Genomic datasets and the tools to analyze them have proliferated at an astonishing rate. However, such tools are often poorly integrated with each other: each program typically produces its own custom output in a variety of non-standard file formats. Here we present glbase, a framework that uses a flexible set of descriptors that can quickly parse non-binary data files. glbase includes many functions to intersect two lists of data, including operations on genomic interval data and support for the efficient random access to huge genomic data files. Many glbase functions can produce graphical outputs, including scatter plots, heatmaps, boxplots and other common analytical displays of high-throughput data such as RNA-seq, ChIP-seq and microarray expression data. glbase is designed to rapidly bring biological data into a Python-based analytical environment to facilitate analysis and data processing. In summary, glbase is a flexible and multifunctional toolkit that allows the combination and analysis of high-throughput data (especially next-generation sequencing and genome-wide data), and which has been instrumental in the analysis of complex data sets. glbase is freely available at <span>http://bitbucket.org/oaxiom/glbase/</span><svg><path></path></svg>.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"3 1","pages":"Article 3:1"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-9769-3-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32824082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}