Cell Regeneration最新文献

{"title":"Genomic and molecular control of cell type and cell type conversions","authors":"Xiuling Fu,&nbsp;Fangfang He,&nbsp;Yuhao Li,&nbsp;Allahverdi Shahveranov,&nbsp;Andrew Paul Hutchins","doi":"10.1016/j.cr.2017.09.001","DOIUrl":"10.1016/j.cr.2017.09.001","url":null,"abstract":"<div><p>Organisms are made of a limited number of cell types that combine to form higher order tissues and organs. Cell types have traditionally been defined by their morphologies or biological activity, yet the underlying molecular controls of cell type remain unclear. The onset of single cell technologies, and more recently genomics (particularly single cell genomics), has substantially increased the understanding of the concept of cell type, but has also increased the complexity of this understanding. These new technologies have added a new genome wide molecular dimension to the description of cell type, with genome-wide expression and epigenetic data acting as a cell type ‘fingerprint’ to describe the cell state. Using these genomic fingerprints cell types are being increasingly defined based on specific genomic and molecular criteria, without necessarily a distinct biological function. In this review, we will discuss the molecular definitions of cell types and cell type control, and particularly how endogenous and exogenous transcription factors can control cell types and cell type conversions.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"6 ","pages":"Pages 1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cr.2017.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35749214","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":"Dissecting microRNA-mediated regulation of stemness, reprogramming, and pluripotency","authors":"Young Jin Lee ,&nbsp;Suresh Ramakrishna ,&nbsp;Himanshu Chauhan ,&nbsp;Won Sun Park ,&nbsp;Seok-Ho Hong ,&nbsp;Kye-Seong Kim","doi":"10.1186/s13619-016-0028-0","DOIUrl":"10.1186/s13619-016-0028-0","url":null,"abstract":"<div><p>Increasing evidence indicates that microRNAs (miRNAs), endogenous short non-coding RNAs 19–24 nucleotides in length, play key regulatory roles in various biological events at the post-transcriptional level. Embryonic stem cells (ESCs) represent a valuable tool for disease modeling, drug discovery, developmental studies, and potential cell-based therapies in regenerative medicine due to their unlimited self-renewal and pluripotency. Therefore, remarkable progress has been made in recent decades toward understanding the expression and functions of specific miRNAs in the establishment and maintenance of pluripotency. Here, we summarize the recent knowledge regarding the regulatory roles of miRNAs in self-renewal of pluripotent ESCs and during cellular reprogramming, as well as the potential role of miRNAs in two distinct pluripotent states (naïve and primed).</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"5 1","pages":"Article 5:2"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-016-0028-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859530","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":"RNA-binding proteins in mouse male germline stem cells: a mammalian perspective","authors":"Huayu Qi","doi":"10.1186/s13619-015-0022-y","DOIUrl":"10.1186/s13619-015-0022-y","url":null,"abstract":"<div><p>Adult stem cells that reside in particular types of tissues are responsible for tissue homeostasis and regeneration. Cellular functions of adult stem cells are intricately related to the gene expression programs in those cells. Past research has demonstrated that regulation of gene expression at the transcriptional level can decisively alter cell fate of stem cells. However, cellular contents of mRNAs are sometimes not equivalent to proteins, the functional units of cells. It is increasingly realized that post-transcriptional and translational regulation of gene expression are also fundamental for stem cell functions. Compared to differentiated somatic cells, effects on cellular status manifested by varied expression of RNA-binding proteins and global protein synthesis have been demonstrated in several stem cell systems. Through the cooperation of both cis-elements of mRNAs and trans-acting RNA-binding proteins that are intimately associated with them, regulation of localization, stability, and translational status of mRNAs directly influences the self-renewal and differentiation of stem cells. Previous studies have uncovered some of the molecular mechanisms that underlie the functions of RNA-binding proteins in stem cells in invertebrate species. However, their roles in adult stem cells in mammals are just beginning to be unveiled. This review highlights some of the RNA-binding proteins that play important functions during the maintenance and differentiation of mouse male germline stem cells, the adult stem cells in the male reproductive organ.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"5 1","pages":"Article 5:1"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0022-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859452","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":"Loss of Mgat5a-mediated N-glycosylation stimulates regeneration in zebrafish","authors":"Wuhong Pei ,&nbsp;Sunny C. Huang ,&nbsp;Lisha Xu ,&nbsp;Kade Pettie ,&nbsp;María Laura Ceci ,&nbsp;Mario Sánchez ,&nbsp;Miguel L. Allende ,&nbsp;Shawn M. Burgess","doi":"10.1186/s13619-016-0031-5","DOIUrl":"10.1186/s13619-016-0031-5","url":null,"abstract":"<div><h3>Background</h3><p>We are using genetics to identify genes specifically involved in hearing regeneration. In a large-scale genetic screening, we identified <em>mgat5a</em>, a gene in the <em>N</em>-glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration.</p></div><div><h3>Methods</h3><p>We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish. We used pharmacological inhibition of <em>N</em>-glycosylation by swansonine. We also used over-expression analysis by mRNA injections to demonstrate how changes in <em>N</em>-glycosylation can alter cell signaling.</p></div><div><h3>Results</h3><p>We found that <em>mgat5a</em> was expressed in multiple tissues during zebrafish embryo development, particularly enriched in neural tissues including the brain, retina, and lateral line neuromasts. An <em>mgat5a</em> insertional mutation and a CRISPR/Cas9-generated truncation mutation both caused an enhancement of hair cell regeneration which could be phenocopied by pharmacological inhibition with swansonine. In addition to hair cell regeneration, inhibition of the <em>N</em>-glycosylation pathway also enhanced the regeneration of lateral line axon and caudal fins. Further analysis showed that <em>N</em>-glycosylation altered the responsiveness of TGF-beta signaling.</p></div><div><h3>Conclusions</h3><p>The findings from this study provide experimental evidence for the involvement of <em>N</em>-glycosylation in tissue regeneration and cell signaling.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"5 1","pages":"Article 5:3"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-016-0031-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859558","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":"Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells: current state of the art","authors":"Eleni Oberbauer ,&nbsp;Carolin Steffenhagen ,&nbsp;Christoph Wurzer ,&nbsp;Christian Gabriel ,&nbsp;Heinz Redl ,&nbsp;Susanne Wolbank","doi":"10.1186/s13619-015-0020-0","DOIUrl":"10.1186/s13619-015-0020-0","url":null,"abstract":"<div><p>In the past decade, adipose tissue became a highly interesting source of adult stem cells for plastic surgery and regenerative medicine. The isolated stromal vascular fraction (SVF) is a heterogeneous cell population including the adipose-derived stromal/stem cells (ASC), which showed regenerative potential in several clinical studies and trials. SVF should be provided in a safe and reproducible manner in accordance with current good manufacturing practices (cGMP). To ensure highest possible safety for patients, a precisely defined procedure with a high-quality control is required. Hence, an increasing number of adipose tissue-derived cell isolation systems have been developed. These systems aim for a closed, sterile, and safe isolation process limiting donor variations, risk for contaminations, and unpredictability of the cell material. To isolate SVF from adipose tissue, enzymes such as collagenase are used. Alternatively, in order to avoid enzymes, isolation systems using physical forces are available. Here, we provide an overview of known existing enzymatic and non-enzymatic adipose tissue-derived cell isolation systems, which are patented, published, or already on the market.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:7"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0020-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34060781","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":"Regulatory functions and pathological relevance of the MECP2 3′UTR in the central nervous system","authors":"Heather McGowan ,&nbsp;Zhiping P. Pang","doi":"10.1186/s13619-015-0023-x","DOIUrl":"10.1186/s13619-015-0023-x","url":null,"abstract":"<div><p>Methyl-CpG-binding protein 2 (MeCP2), encoded by the gene <em>MECP2</em>, is a transcriptional regulator and chromatin-remodeling protein, which is ubiquitously expressed and plays an essential role in the development and maintenance of the central nervous system (CNS). Highly enriched in post-migratory neurons, MeCP2 is needed for neuronal maturation, including dendritic arborization and the development of synapses. Loss-of-function mutations in <em>MECP2</em> cause Rett syndrome (RTT), a debilitating neurodevelopmental disorder characterized by a phase of normal development, followed by the progressive loss of milestones and cognitive disability. While a great deal has been discovered about the structure, function, and regulation of MeCP2 in the time since its discovery as the genetic cause of RTT, including its involvement in a number of RTT-related syndromes that have come to be known as MeCP2-spectrum disorders, much about this multifunctional protein remains enigmatic. One unequivocal fact that has become apparent is the importance of maintaining MeCP2 protein levels within a narrow range, the limits of which may depend upon the cell type and developmental time point. As such, MeCP2 is amenable to complex, multifactorial regulation. Here, we summarize the role of the <em>MECP2</em> 3' untranslated region (UTR) in the regulation of MeCP2 protein levels and how mutations in this region contribute to autism and other non-RTT neuropsychiatric disorders.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:9"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0023-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34131104","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 barriers and enhancers: strategies to enhance the efficiency and kinetics of induced pluripotency","authors":"Behnam Ebrahimi","doi":"10.1186/s13619-015-0024-9","DOIUrl":"10.1186/s13619-015-0024-9","url":null,"abstract":"<div><p>Induced pluripotent stem cells are powerful tools for disease modeling, drug screening, and cell transplantation therapies. These cells can be generated directly from somatic cells by ectopic expression of defined factors through a reprogramming process. However, pluripotent reprogramming is an inefficient process because of various defined and unidentified barriers. Recent studies dissecting the molecular mechanisms of reprogramming have methodically improved the quality, ease, and efficiency of reprogramming. Different strategies have been applied for enhancing reprogramming efficiency, including depletion/inhibition of barriers (p53, p21, p57, p16^Ink4a/p19^Arf, Mbd3, etc.), overexpression of enhancing genes (e.g., <em>FOXH1</em>, <em>C/EBP alpha</em>, <em>UTF1</em>, and <em>GLIS1</em>), and administration of certain cytokines and small molecules. The current review provides an in-depth overview of the cutting-edge findings regarding distinct barriers of reprogramming to pluripotency and strategies to enhance reprogramming efficiency. By 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.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:10"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0024-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859473","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 aging in adult progeria","authors":"Hoi-Hung Cheung ,&nbsp;Duanqing Pei ,&nbsp;Wai-Yee Chan","doi":"10.1186/s13619-015-0021-z","DOIUrl":"10.1186/s13619-015-0021-z","url":null,"abstract":"<div><p>Aging is considered an irreversible biological process and also a major risk factor for a spectrum of geriatric diseases. Advanced age-related decline in physiological functions, such as neurodegeneration, development of cardiovascular disease, endocrine and metabolic dysfunction, and neoplastic transformation, has become the focus in aging research. Natural aging is not regarded as a programmed process. However, accelerated aging due to inherited genetic defects in patients of progeria is programmed and resembles many aspects of natural aging. Among several premature aging syndromes, Werner syndrome (WS) and Hutchinson–Gilford progeria syndrome (HGPS) are two broadly investigated diseases. In this review, we discuss how stem cell aging in WS helps us understand the biology of aging. We also discuss briefly how the altered epigenetic landscape in aged cells can be reversed to a “juvenile” state. Lastly, we explore the potential application of the latest genomic editing technique for stem cell-based therapy and regenerative medicine in the context of aging.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:6"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0021-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34060780","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":"GATA2−/− human ESCs undergo attenuated endothelial to hematopoietic transition and thereafter granulocyte commitment","authors":"Ke Huang ,&nbsp;Juan Du ,&nbsp;Ning Ma ,&nbsp;Jiajun Liu ,&nbsp;Pengfei Wu ,&nbsp;Xiaoya Dong ,&nbsp;Minghui Meng ,&nbsp;Wenqian Wang ,&nbsp;Xin Chen ,&nbsp;Xi Shi ,&nbsp;Qianyu Chen ,&nbsp;Zhongzhou Yang ,&nbsp;Shubin Chen ,&nbsp;Jian Zhang ,&nbsp;Yuhang Li ,&nbsp;Wei Li ,&nbsp;Yi Zheng ,&nbsp;Jinglei Cai ,&nbsp;Peng Li ,&nbsp;Xiaofang Sun ,&nbsp;Guangjin Pan","doi":"10.1186/s13619-015-0018-7","DOIUrl":"10.1186/s13619-015-0018-7","url":null,"abstract":"<div><h3>Background</h3><p>Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcription factors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesis in mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially during early embryonic development stage, is largely unknown.</p></div><div><h3>Results</h3><p>To examine the role of GATA2 in human background, we generated homozygous <em>GATA2</em> knockout human embryonic stem cells (<em>GATA2</em>^{<em>−/−</em>} hESCs) and analyzed their blood differentiation potential. Our results demonstrated that <em>GATA2</em>^{<em>−/−</em>} hESCs displayed attenuated generation of CD34⁺CD43⁺ hematopoietic progenitor cells (HPCs), due to the impairment of endothelial to hematopoietic transition (EHT). Interestingly, <em>GATA2</em>^{<em>−/−</em>} hESCs retained the potential to generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulation was partially responsible for the defects of <em>GATA2</em>^{<em>−/−</em>} hESCs in generation of CD34⁺CD43⁺ HPCs and granulocytes. Furthermore, we found that <em>GATA2</em>^{<em>−/−</em>} hESCs restored the granulocyte potential in the presence of Notch signaling.</p></div><div><h3>Conclusion</h3><p>Our findings revealed the essential roles of GATA2 in EHT and granulocyte development through regulating <em>SPI1</em>, and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled by human ESCs.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:4"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0018-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34070141","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":"Vascularization mediated by mesenchymal stem cells from bone marrow and adipose tissue: a comparison","authors":"Karoline Pill ,&nbsp;Sandra Hofmann ,&nbsp;Heinz Redl ,&nbsp;Wolfgang Holnthoner","doi":"10.1186/s13619-015-0025-8","DOIUrl":"10.1186/s13619-015-0025-8","url":null,"abstract":"<div><p>Tissue-engineered constructs are promising to overcome shortage of organ donors and to reconstruct at least parts of injured or diseased tissues or organs. However, oxygen and nutrient supply are limiting factors in many tissues, especially after implantation into the host. Therefore, the development of a vascular system prior to implantation appears crucial. To develop a functional vascular system, different cell types that interact with each other need to be co-cultured to simulate a physiological environment in vitro. This review provides an overview and a comparison of the current knowledge of co-cultures of human endothelial cells (ECs) with human adipose tissue-derived stem/stromal cells (ASCs) or bone marrow-mesenchymal stem cells (BMSCs) in three dimensional (3D) hydrogel matrices. Mesenchymal stem cells (MSCs), BMSCs or ASCs, have been shown to enhance vascular tube formation of ECs and to provide a stabilizing function in addition to growth factor delivery and permeability control for ECs. Although phenotypically similar, MSCs from different tissues promote tubulogenesis through distinct mechanisms. In this report, we describe differences and similarities regarding molecular interactions in order to investigate which of these two cell types displays more favorable characteristics to be used in clinical applications. Our comparative study shows that ASCs as well as BMSCs are both promising cell types to induce vascularization with ECs in vitro and consequently are promising candidates to support in vivo vascularization.</p></div>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"4 1","pages":"Article 4:8"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13619-015-0025-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34115542","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}