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1.
Bleul CC  Corbeaux T  Reuter A  Fisch P  Mönting JS  Boehm T 《Nature》2006,441(7096):992-996
The thymus is essential for the generation of self-tolerant effector and regulatory T cells. Intrathymic T-cell development requires an intact stromal microenvironment, of which thymic epithelial cells (TECs) constitute a major part. For instance, cell-autonomous genetic defects of forkhead box N1 (Foxn1) and autoimmune regulator (Aire) in thymic epithelial cells cause primary immunodeficiency and autoimmunity, respectively. During development, the thymic epithelial rudiment gives rise to two major compartments, the cortex and medulla. Cortical TECs positively select T cells, whereas medullary TECs are involved in negative selection of potentially autoreactive T cells. It has long been unclear whether these two morphologically and functionally distinct types of epithelial cells arise from a common bi-potent progenitor cell and whether such progenitors are still present in the postnatal period. Here, using in vivo cell lineage analysis in mice, we demonstrate the presence of a common progenitor of cortical and medullary TECs after birth. To probe the function of postnatal progenitors, a conditional mutant allele of Foxn1 was reverted to wild-type function in single epithelial cells in vivo. This led to the formation of small thymic lobules containing both cortical and medullary areas that supported normal thymopoiesis. Thus, single epithelial progenitor cells can give rise to a complete and functional thymic microenvironment, suggesting that cell-based therapies could be developed for thymus disorders.  相似文献   

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通过克隆形成能力实验以及体内移植实验,发现当敲除小鼠MLL-AF9细胞中的受体结合蛋白1(RIP1)基因后,相对于WT MLL-AF9细胞,其克隆形成能力明显减弱,移植后小鼠生存时间延长了3倍以上.在组织切片观察中,WT MLL-AF9细胞移植小鼠出现明显白血病发病特征,而RIP1~(-/-)MLL-AF9细胞移植小鼠的切片显示正常.当将RIP1中的激酶活性位点突变后,相对于WT MLL-AF9细胞,在移植实验中小鼠生存时间明显延长.对病发小鼠的脾脏细胞流式分析结果表明:激酶活性位点突变后致病能力明显减弱,提示RIP1基因的缺失会导致MLL-AF9致病能力减弱.  相似文献   

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同时分离和培养兔外周血平滑肌祖细胞(SPC)和内皮祖细胞(EPC),为组织工程膀胱的构建和血管化提供种子细胞.分离新西兰兔外周血中的单个核细胞,分别进行SPC和EPC的分离和培养;同时,培养兔膀胱平滑肌细胞(BSMC)作为对照.细胞爬片,观察细胞摄取Dil-AcLDL和结合FITC-UEA-1的能力;间接免疫荧光染色观察平滑肌肌动蛋白(SMA)、结蛋白(Desmin)、KDR、eNOS和vWF的表达情况;进行细胞增殖实验,观察PDGF-BB,VEGF对SPC和EPC的增殖作用.结果发现,培养1周后出现SPC克隆和EPC克隆,SPC呈梭形,长短不一;EPC形态均一,呈典型的鹅卵石形;培养的BSMC形态均一,为长梭形,呈峰谷样形态.利用克隆环分离SPC和EPC克隆,继续培养可得到高纯度的SPC和EPC.SPC不摄取Dil-AcLDL,不结合FITC-UEA-1;SPC表达SMA、Desmin和KDR,不表达eNOS和vWF.EPC同时摄取Dil-AcLDL和结合FITC-UEA-1;EPC表达eNOS、vWF和KDR,不表达SMA和Desmin.BSMC仅表达SMA和Desmin.PDGF-BB仅能促进SPC增殖...  相似文献   

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The skin interfollicular epidermis (IFE) is the first barrier against the external environment and its maintenance is critical for survival. Two seemingly opposite theories have been proposed to explain IFE homeostasis. One posits that IFE is maintained by long-lived slow-cycling stem cells that give rise to transit-amplifying cell progeny, whereas the other suggests that homeostasis is achieved by a single committed progenitor population that balances stochastic fate. Here we probe the cellular heterogeneity within the IFE using two different inducible Cre recombinase–oestrogen receptor constructs targeting IFE progenitors in mice. Quantitative analysis of clonal fate data and proliferation dynamics demonstrate the existence of two distinct proliferative cell compartments arranged in a hierarchy involving slow-cycling stem cells and committed progenitor cells. After wounding, only stem cells contribute substantially to the repair and long-term regeneration of the tissue, whereas committed progenitor cells make a limited contribution.  相似文献   

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从金融管理者的角度研究了资产证券化的兴起会带来什么样的问题和挑战。  相似文献   

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N Yamamoto  T Matsumoto  Y Koyanagi  Y Tanaka  Y Hinuma 《Nature》1982,299(5881):367-369
Members of three distinct classes of animal virus have been associated with naturally occurring neoplasias in man: Epstein--Barr virus (EBV), a DNA virus belonging to herpesvirus group, papillomavirus, and a novel human RNA (retro) virus, human T-cell leukemia virus or adult T-cell leukaemia (ATL) virus. We have established seven continuous cell lines from ATL patients and 0.1-7% of these cells consistently express ATL-specific antigens (ATLA). EBV-associated nuclear antigen (EBNA) is also found in more than 90% of these cells. We have cloned cells from two of these lines and show here that both ATLA and EBNA were present in the same B-cell clone carrying surface immunoglobulin (sIg).  相似文献   

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微囊化基质细胞对脐带血造血干/祖细胞扩增支持   总被引:1,自引:0,他引:1  
将脐带血单个核细胞与包埋有兔骨髓间充质干细胞的海藻酸钙微胶珠在3种不同的培养液中进行了7d的体外静态共培养.每24h进行总有核细胞计数,在0、72和168h进行流式CD34+细胞分析以及甲基纤维素集落检验.实验结果表明:经过7d的静态共培养,在添加常规剂量造血生长因子的培养液中,总有核细胞扩增了(15±2.85)倍,CD34+细胞扩增了(5.33±0.32)倍,CFU-Cs扩增了(5.6±1.21)倍.微胶囊可以作为一种新的共培养隔离手段,微囊化兔骨髓间充质干细胞在添加适量血清或者造血生长因子组合的条件下对于脐带血造血干/祖细胞在静态下的扩增有明显的促进作用.  相似文献   

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概述了MARC元数据和DC元数据,分析了MARC向DC转换的必要性.同时利用现有的映射关系表,基于JAVA编程语言实现了MARC向DC的转换,演示了程序的运行过程并分析了转换程序的主要思路.  相似文献   

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不随时间变化的电荷所产生的静电场以及由传导电流所产生的恒流磁场属于静态场,而随时间变化的电荷以及传导电流就会产生交变场.这种变化的电场和磁场就不能通过静态场简单的规律来解释.麦克斯韦方程组是交变电磁场理论的核心.本文详细地介绍了麦克斯韦方程组的形成及推导,使读者能够轻松地完成从静态场到交变场的转变,并对交变电磁场理论有更深的理解.  相似文献   

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Klimanskaya I  Chung Y  Becker S  Lu SJ  Lanza R 《Nature》2006,444(7118):481-485
The derivation of human embryonic stem (hES) cells currently requires the destruction of ex utero embryos. A previous study in mice indicates that it might be possible to generate embryonic stem (ES) cells using a single-cell biopsy similar to that used in preimplantation genetic diagnosis (PGD), which does not interfere with the embryo's developmental potential. By growing the single blastomere overnight, the resulting cells could be used for both genetic testing and stem cell derivation without affecting the clinical outcome of the procedure. Here we report a series of ten separate experiments demonstrating that hES cells can be derived from single blastomeres. In this proof-of-principle study, multiple biopsies were taken from each embryo using micromanipulation techniques and none of the biopsied embryos were allowed to develop in culture. Nineteen ES-cell-like outgrowths and two stable hES cell lines were obtained. The latter hES cell lines maintained undifferentiated proliferation for more than eight months, and showed normal karyotype and expression of markers of pluripotency, including Oct-4, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, nanog and alkaline phosphatase. These cells retained the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. The ability to create new stem cell lines and therapies without destroying embryos would address the ethical concerns of many, and allow the generation of matched tissue for children and siblings born from transferred PGD embryos.  相似文献   

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Brunet A  Rando TA 《Nature》2007,449(7160):288-291
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给出了函数式语言到过程式语言转换的关键技术,即抽象论域到具体数据结构的转换技术.抽象论域的转换是抽象表达式到具体表达式转换、模式匹配处理的前提.函数式语言到过程式语言的转换,解决了函数式语言在具体实现和时间方面存在的大量动态函数复制的问题.这种转换技术可用于开发指称语义到解释器、指称语义到编译器、属性文法到过程式语言、属性文法到YACC(Yet Another Computer Compilier)输入文件的各种自动生成器.  相似文献   

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该文在传统线模型的基础上,建立了新的线—面混合模型,并通过对混合模型的自动消隐,实现线模型的消隐。所提算法均已在IBM/PC机上用TURBO PASCAL语言实现。  相似文献   

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