共查询到20条相似文献,搜索用时 15 毫秒
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Giulia Schiroli Anastasia Conti Samuele Ferrari Lucrezia della Volpe Aurelien Jacob Luisa Albano Stefano Beretta Andrea Calabria Valentina Vavassori Patrizia Gasparini Eralda Salataj Delphine Ndiaye-Lobry Chiara Brombin Julie Chaumeil Eugenio Montini Ivan Merelli Pietro Genovese Luigi Naldini Raffaella Di Micco 《Cell Stem Cell》2019,24(4):551-565.e8
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Julia M. Kr?pfl Ingeborg Stelzer Harald Mangge Karin Pekovits Robert Fuchs Nathalie Allard Lukas Schinagl Peter Hofmann Gottfried Dohr Sandra Wallner-Liebmann Wolfgang Domej Wolfram Müller 《PloS one》2014,9(9)
A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/−4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15). The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI), cortisol (Co) and interleukin-6 (IL-6). Additionally, the influence of exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n = 6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality. 相似文献
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《Cell cycle (Georgetown, Tex.)》2013,12(18):2201-2204
Hematopoietic stem cells (HSC) are undifferentiated cells, which self-renew over a long period of time and give rise to committed hematopoietic progenitor cells (HPC) containing the capability to replenish the whole blood system. Since both uncontrolled expansion as well as loss of HSC would be fatal, the decision of self-renewal versus differentiation needs to be tightly controlled. There is good evidence that both HSC niches as well as asymmetric cell divisions are involved in controlling whether HSC self-renew or become committed to differentiate. In this context, we recently identified four proteins which frequently segregate asymmetrically in dividing HSC/HPC. Remarkably, three of these proteins, the tetraspanins CD53 and CD63, and the transferrin receptor are endosome-associated proteins. Here, we highlight these observations in conjunction with recent findings in model organisms which show that components of the endosomal machinery are involved in cell-fate specification processes. 相似文献
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在模拟骨髓造血壁龛(hematopoietic niche)的氧分压条件下,探讨微囊化成骨细胞(osteoblasts,OB)对脐血造血干/祖细胞(HSPC)体外扩增的支持和调控机理.分离培养人髂骨OB,采用聚电解质络合法将第3代的OB以密度为8×105 ml包埋在直径为0.5 mm的明胶-海藻酸钠-壳聚糖(GAC)微胶珠中.将微珠+造血干/祖细胞(A′组)、造血干/祖细胞(B′组)及微珠(C′组)置于6孔板,在5%氧分压下进行培养.同时在20%常氧条件下设置同样分组培养作为对照(A,B,C).通过流式细胞分析和半固体细胞集落培养,观察比较各培养体系中造血干/祖细胞的扩增,并检测体系内白血病抑制因子(LIF)和白介素-6(IL-6)的含量变化以探讨作用机理.经过倒置相差显微镜观察,人成骨细胞在微珠中分散均匀,生长状态良好.微珠内部有丰富的孔道供营养物质传递,有大量造血干/祖细胞弱黏附于微珠表面.经过7天的培养,A′、B′、A、B四组造血细胞的扩增倍数分别为(49.0 ± 4.6),(3.3 ± 0.5),(17.7 ± 1.2)和(1.9 ± 0.2).A′、B′、A 组的CD34+细胞分别扩增了(87.6 ± 8.3), (2.2 ± 0.3)和(14.9 ± 1.0)倍,B组则出现下降.A′、B′、A、B四组CFU-Cs集落扩增倍数分别为(9.8 ± 0.8),(3.5 ± 0.4), (6.9 ± 0.7)和(2.6 ± 0.2).低氧共培养体系比常氧共培养体系和非共培养体系对造血干/祖细胞的扩增有更大的促进作用.A′、B′、C′中IL-6和LIF含量明显高于对应的A、B、C组,与扩增倍数的差异相对应.微囊化成骨细胞对造血干/祖细胞扩增有明显的促进作用,5%氧分压接近体内造血壁龛氧环境,在此环境中成骨细胞分泌细胞因子量增多并通过其对造血干/祖细胞的扩增进行调节. 相似文献
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H. Angharad Watson Rebecca J. Holley Kia J. Langford-Smith Fiona L. Wilkinson Toin H. van Kuppevelt Robert F. Wynn J. Edmond Wraith Catherine L. R. Merry Brian W. Bigger 《The Journal of biological chemistry》2014,289(52):36194-36203
Mucopolysaccharidosis I Hurler (MPSI-H) is a pediatric lysosomal storage disease caused by genetic deficiencies in IDUA, coding for α-l-iduronidase. Idua−/− mice share similar clinical pathology with patients, including the accumulation of the undegraded glycosaminoglycans (GAGs) heparan sulfate (HS), and dermatan sulfate (DS), progressive neurodegeneration, and dysostosis multiplex. Hematopoietic stem cell transplantation (HSCT) is the most effective treatment for Hurler patients, but reduced intensity conditioning is a risk factor in transplantation, suggesting an underlying defect in hematopoietic cell engraftment. HS is a co-receptor in the CXCL12/CXCR4 axis of hematopoietic stem and progenitor cell (HSPC) migration to the bone marrow (BM), but the effect of HS alterations on HSPC migration, or the functional role of HS in MPSI-H are unknown. We demonstrate defective WT HSPC engraftment and migration in Idua−/− recipient BM, particularly under reduced intensity conditioning. Both intra- but especially extracellular Idua−/− BM HS was significantly increased and abnormally sulfated. Soluble heparinase-sensitive GAGs from Idua−/− BM and specifically 2-O-sulfated HS, elevated in Idua−/− BM, both inhibited CXCL12-mediated WT HSPC transwell migration, while DS had no effect. Thus we have shown that excess overly sulfated extracellular HS binds, and sequesters CXCL12, limiting hematopoietic migration and providing a potential mechanism for the limited scope of HSCT in Hurler disease. 相似文献
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Li Ping Jiang Hualian Peng Hong Zeng Weijie Zhong Yongheng He Miao Xie Luyang Chen Junhai Guo Deyin Wu Junyu Li Chun-Mei 《中国病毒学》2021,36(6):1411-1420
Virologica Sinica - Zika virus (ZIKV) infection could disrupt neurogenesis and cause microcephaly in neonates by targeting neural progenitor cells (NPCs). The tumor suppressor p53-mediated cell... 相似文献
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Florian Noulin Javed Karim Manesia Anna Rosanas-Urgell Annette Erhart Céline Borlon Jan Van Den Abbeele Umberto d'Alessandro Catherine M. Verfaillie 《PloS one》2014,9(11)
The predilection of Plasmodium vivax (P. vivax) for reticulocytes is a major obstacle for its establishment in a long-term culture system, as this requires a continuous supply of large quantities of reticulocytes, representing only 1–2% of circulating red blood cells. We here compared the production of reticulocytes using an established in vitro culture system from three different sources of hematopoietic stem/progenitor cells (HSPC), i.e. umbilical cord blood (UCB), bone marrow (BM) and adult peripheral blood (PB). Compared to CD34+-enriched populations of PB and BM, CD34+-enriched populations of UCB produced the highest amount of reticulocytes that could be invaded by P. vivax. In addition, when CD34+-enriched cells were first expanded, a further extensive increase in reticulocytes was seen for UCB, to a lesser degree BM but not PB. As invasion by P. vivax was significantly better in reticulocytes generated in vitro, we also suggest that P. vivax may have a preference for invading immature reticulocytes, which should be confirmed in future studies. 相似文献
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Grigori G. Prikhodko Yan Wang Ella Freulich Carol Prives Lois K. Miller 《Journal of virology》1999,73(2):1227-1234
In vertebrates, p53 participates in numerous biological processes including cell cycle regulation, apoptosis, differentiation, and oncogenic transformation. When insect SF-21 cells were infected with a recombinant of the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) overexpressing human p53, p53 formed a stable complex with the product of the AcMNPV orf92, a novel protein p33. The interaction between p53 and p33 was further confirmed by immunoprecipitation studies. When individually expressed in SF-21 cells, human p53 localized mainly in the nucleus whereas baculovirus p33 displayed diffuse cytoplasmic staining and punctuate nuclear staining. However, coexpression of p33 with p53 resulted in exclusive nuclear localization of p33. In both SF-21 and TN-368 cells, p53 expression induced typical features of apoptosis including nuclear condensation and fragmentation, oligonucleosomal ladder formation, cell surface blebbing, and apoptotic body formation. Coexpression of p53 with a baculovirus inhibitor of apoptosis, p35, OpIAP, or CpIAP, blocked apoptosis, whereas coexpression with p33 enhanced p53-mediated apoptosis approximately twofold. Expression of p53 in SF-21 cells stably expressing OpIAP inhibited cell growth in the presence or absence of p33. Thus, human p53 can influence both insect cell growth and death and baculovirus p33 can modulate the death-inducing effects of p53. 相似文献
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Linghua Zhou Yong Shen Libo Jiang Danni Yin Jingxin Guo Hui Zheng Hao Sun Rongling Wu Yunqian Guo 《PloS one》2015,10(5)
Cells with the same genotype growing under the same conditions can show different phenotypes, which is known as “population heterogeneity”. The heterogeneity of hematopoietic progenitor cells has an effect on their differentiation potential and lineage choices. However, the genetic mechanisms governing population heterogeneity remain unclear. Here, we present a statistical model for mapping the quantitative trait locus (QTL) that affects hematopoietic cell heterogeneity. This strategy, termed systems mapping, integrates a system of differential equations into the framework for systems mapping, allowing hypotheses regarding the interplay between genetic actions and cell heterogeneity to be tested. A simulation approach based on cell heterogeneity dynamics has been designed to test the statistical properties of the model. This model not only considers the traditional QTLs, but also indicates the methylated QTLs that can illustrate non-genetic individual differences. It has significant implications for probing the molecular, genetic and epigenetic mechanisms of hematopoietic progenitor cell heterogeneity. 相似文献
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Lingyu Zeng Chong Chen Guoliang Song Zhiling Yan Shijuan Xu Lu Jia Shuang Ding Jiang Cao Wei Chen Hai Cheng Zhenyu Li Wei Sang Lin Wang Youping Li Kailin Xu 《Cell biochemistry and biophysics》2012,64(3):213-222
Hematopoietic stem cells transplantation (HSCT) causes endothelial cell damage, disrupting hematopoietic microenviroment and leading to various complications. We hypothesized that infusion of endothelial progenitor cells (EPCs) may improve endothelium repair, facilitate hematopoietic reconstitution, and alleviate complications associated with HSCT. C57Bl6, and BALB/c mice received total body irradiation followed by infusion of C57Bl6-derived bone marrow (BM) cells, with or without concomitant infusion of C57Bl6-derived EPCs. The time course of hematopoietic and immune reconstitution and the severity of the graft-versus-host disease (GVHD) were monitored. Further, to confirm that EPCs promote endothelial cell recovery, HSCT mice were treated with anti-VE-cadherin antibody targeting the endothelium. The EPCs-treated mice exhibited accelerated recovery of BM vasculature, cellularity, hematopoietic stem and progenitor cell recovery, improved counts of lymphocyte subsets in peripheral blood, and facilitated spleen structure reconstruction. EPCs infusion also ameliorated the GVHD in the C57Bl6????BALB/c allo-HSCT model. Systemic administration of anti-VE-cadherin antibody significantly delayed hematological and immune reconstitution in the EPCs-infused mice. In conclusion, our data demonstrate that infusion of EPCs augments the hematopoietic and immune reconstitution, and alleviates the GVHD. These findings further highlight the relationship between the microvascular recovery, hematopoietic and immune reconstitution, and the GVHD. 相似文献
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Bérengère de Laval Patrycja Pawlikowska Laurence Petit-Cocault Chrystèle Bilhou-Nabera Geneviève Aubin-Houzelstein Michèle Souyri Frédéric Pouzoulet Murielle Gaudry Françoise Porteu 《Cell Stem Cell》2013,12(1):37-48
Highlights? Mpl loss increases γ-irradiation-induced genomic instability in HSPCs ? TPO promotes DNA repair in vitro and in vivo in HSPCs ? TPO increases DNA-PK activity and NHEJ-mediated repair efficiency in HSPCs ? A single TPO injection before mouse TBI limits long-term HSC injury and mutagenesis 相似文献
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Ziming Cheng Ting Zhou Azhar Merchant Thomas J. Prihoda Brian L. Wickes Guogang Xu Christi A. Walter Vivienne I. Rebel 《Journal of visualized experiments : JoVE》2014,(84)
In recent years, it has become apparent that genomic instability is tightly related to many developmental disorders, cancers, and aging. Given that stem cells are responsible for ensuring tissue homeostasis and repair throughout life, it is reasonable to hypothesize that the stem cell population is critical for preserving genomic integrity of tissues. Therefore, significant interest has arisen in assessing the impact of endogenous and environmental factors on genomic integrity in stem cells and their progeny, aiming to understand the etiology of stem-cell based diseases.LacI transgenic mice carry a recoverable λ phage vector encoding the LacI reporter system, in which the LacI gene serves as the mutation reporter. The result of a mutated LacI gene is the production of β-galactosidase that cleaves a chromogenic substrate, turning it blue. The LacI reporter system is carried in all cells, including stem/progenitor cells and can easily be recovered and used to subsequently infect E. coli. After incubating infected E. coli on agarose that contains the correct substrate, plaques can be scored; blue plaques indicate a mutant LacI gene, while clear plaques harbor wild-type. The frequency of blue (among clear) plaques indicates the mutant frequency in the original cell population the DNA was extracted from. Sequencing the mutant LacI gene will show the location of the mutations in the gene and the type of mutation.The LacI transgenic mouse model is well-established as an in vivo mutagenesis assay. Moreover, the mice and the reagents for the assay are commercially available. Here we describe in detail how this model can be adapted to measure the frequency of spontaneously occurring DNA mutants in stem cell-enriched Lin-IL7R-Sca-1+cKit++(LSK) cells and other subpopulations of the hematopoietic system. 相似文献
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Yingmei Feng Sarah Schouteden Rachel Geenens Vik Van Duppen Paul Herijgers Paul Holvoet Paul P. Van Veldhoven Catherine M. Verfaillie 《PloS one》2012,7(11)