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1.
Clinically successful hematopoietic cell transplantation is dependent on hematopoietic stem and progenitor cells. Here we identify the matricellular protein Nephroblastoma Overexpressed (Nov, CCN3) as being essential for their functional integrity. Nov expression is restricted to the primitive (CD34) compartments of umbilical vein cord blood, and its knockdown in these cells by lentivirus-mediated RNA interference abrogates their function in vitro and in vivo. Conversely, forced expression of Nov and addition of recombinant Nov protein both enhance primitive stem and/or progenitor activity. Taken together, our results identify Nov (CCN3) as a regulator of human hematopoietic stem or progenitor cells. 相似文献
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Recognition of HLA-A2 by cytotoxic T lymphocytes after DNA transfer into human and murine cells 总被引:3,自引:0,他引:3
M van de Rijn C Bernabeu B Royer-Pokora J Weiss J G Seidman J de Vries H Spits C Terhorst 《Science (New York, N.Y.)》1984,226(4678):1083-1085
A gene coding for the major histocompatibility antigen HLA-A2 was transferred into human HLA-A2 negative M1 cells and murine L cells. Following transfection, these cells expressed molecules at the cell surface that are biochemically indistinguishable from HLA-A2 antigens on the human cell line JY from which the HLA-A2 gene was isolated. The M1A2 cells were recognized and lysed by a cytolytic T-cell clone specific for HLA-A2. The transfected L cells which express HLA-A2 in association with human beta 2-microglobulin were not lysed by this T-cell clone. The specific cytolysis of M1A2 cells could be inhibited by monoclonal antibodies to HLA-A2, and monoclonal antibodies to T3, T8, and LFA-1 on cytotoxic T lymphocytes. These results suggest that killing by allospecific T cells requires HLA-A2 antigens as well as other species-specific structures on the target cell surface. 相似文献
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Site-specific gene expression in vivo by direct gene transfer into the arterial wall 总被引:59,自引:0,他引:59
A recombinant beta-galactosidase gene has been expressed in a specific arterial segment in vivo by direct infection with a murine amphotropic retroviral vector or by DNA transfection with the use of liposomes. Several cell types in the vessel wall were transduced, including endothelial and vascular smooth muscle cells. After retroviral infection, a recombinant reporter gene was expressed for at least 5 months, and no helper virus was detected. Recombinant gene expression achieved by direct retroviral infection or liposome-mediated DNA transfection was limited to the site of infection and was absent from liver, lung, kidney, and spleen. These results demonstrate that site-specific gene expression can be achieved by direct gene transfer in vivo and could be applied to the treatment of such human diseases as atherosclerosis or cancer. 相似文献
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Chan AW Chong KY Martinovich C Simerly C Schatten G 《Science (New York, N.Y.)》2001,291(5502):309-312
Transgenic rhesus monkeys carrying the green fluorescent protein (GFP) gene were produced by injecting pseudotyped replication-defective retroviral vector into the perivitelline space of 224 mature rhesus oocytes, later fertilized by intracytoplasmic sperm injection. Of the three males born from 20 embryo transfers, one was transgenic when accessible tissues were assayed for transgene DNA and messenger RNA. All tissues that were studied from a fraternal set of twins, miscarried at 73 days, carried the transgene, as confirmed by Southern analyses, and the GFP transgene reporter was detected by both direct and indirect fluorescence imaging. 相似文献
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A murine beta-thalassemia was corrected by the transfer of cloned beta-globin genes into the mouse germ line. The cloned mouse beta maj-globin gene or the cloned human beta-globin gene was introduced into mice deficient in beta-globin synthesis because of a deletion of the beta maj-globin gene. Both introduced genes produced functional beta-globin chains, leading to a reduction in one case, and elimination in another case, of the anemia and associated abnormalities of the red blood cells. 相似文献
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Manganas LN Zhang X Li Y Hazel RD Smith SD Wagshul ME Henn F Benveniste H Djuric PM Enikolopov G Maletic-Savatic M 《Science (New York, N.Y.)》2007,318(5852):980-985
The identification of neural stem and progenitor cells (NPCs) by in vivo brain imaging could have important implications for diagnostic, prognostic, and therapeutic purposes. We describe a metabolic biomarker for the detection and quantification of NPCs in the human brain in vivo. We used proton nuclear magnetic resonance spectroscopy to identify and characterize a biomarker in which NPCs are enriched and demonstrated its use as a reference for monitoring neurogenesis. To detect low concentrations of NPCs in vivo, we developed a signal processing method that enabled the use of magnetic resonance spectroscopy for the analysis of the NPC biomarker in both the rodent brain and the hippocampus of live humans. Our findings thus open the possibility of investigating the role of NPCs and neurogenesis in a wide variety of human brain disorders. 相似文献
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Rabovsky D 《Science (New York, N.Y.)》1971,174(4012):933-934
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Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment 总被引:1,自引:0,他引:1
Notta F Doulatov S Laurenti E Poeppl A Jurisica I Dick JE 《Science (New York, N.Y.)》2011,333(6039):218-221
Lifelong blood cell production is dependent on rare hematopoietic stem cells (HSCs) to perpetually replenish mature cells via a series of lineage-restricted intermediates. Investigating the molecular state of HSCs is contingent on the ability to purify HSCs away from transiently engrafting cells. We demonstrated that human HSCs remain infrequent, using current purification strategies based on Thy1 (CD90) expression. By tracking the expression of several adhesion molecules in HSC-enriched subsets, we revealed CD49f as a specific HSC marker. Single CD49f(+) cells were highly efficient in generating long-term multilineage grafts, and the loss of CD49f expression identified transiently engrafting multipotent progenitors (MPPs). The demarcation of human HSCs and MPPs will enable the investigation of the molecular determinants of HSCs, with a goal of developing stem cell-based therapeutics. 相似文献
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Chimeric nucleases stimulate gene targeting in human cells 总被引:1,自引:0,他引:1
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Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow 总被引:40,自引:0,他引:40
T M Folks S W Kessler J M Orenstein J S Justement E S Jaffe A S Fauci 《Science (New York, N.Y.)》1988,242(4880):919-922
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Manganas et al. (Reports, 9 November 2007, p. 980) used nuclear magnetic resonance spectroscopy to identify a biomarker of neural progenitor cells. However, their analysis relies on spectral processing methods that are known to be problematic. Absent detection using alternate methods of spectrum analysis or controls to quantify the false discovery rate, their conclusions may be premature. 相似文献
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Phillips RL Ernst RE Brunk B Ivanova N Mahan MA Deanehan JK Moore KA Overton GC Lemischka IR 《Science (New York, N.Y.)》2000,288(5471):1635-1640
Blood cell production originates from a rare population of multipotent, self-renewing stem cells. A genome-wide gene expression analysis was performed in order to define regulatory pathways in stem cells as well as their global genetic program. Subtracted complementary DNA libraries from highly purified murine fetal liver stem cells were analyzed with bioinformatic and array hybridization strategies. A large percentage of the several thousand gene products that have been characterized correspond to previously undescribed molecules with properties suggestive of regulatory functions. The complete data, available in a biological process-oriented database, represent the molecular phenotype of the hematopoietic stem cell. 相似文献
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Transplantation of fetal hematopoietic stem cells in utero: the creation of hematopoietic chimeras 总被引:11,自引:0,他引:11
Transplantation of normal, immature, fetal hematopoietic cells into a preimmune fetal recipient with a congenital hemoglobinopathy may allow partial reconstitution of normal hemoglobin production without the complications associated with postnatal bone marrow transplantation (immunosuppression and the occurrence of graft versus host disease). In order to test this hypothesis the naturally occurring polymorphism at the beta-hemoglobin locus of the sheep was used as a marker for engraftment and hematopoietic chimerism. Intraperitoneal injection of allogeneic fetal stem cells into normal fetal lambs resulted in hematopoietic chimerism in three of four surviving recipients. This chimerism has been sustained for 6 months after birth and 9 months after engraftment, without evidence of graft versus host disease, and without the use of immunosuppressive therapy. 相似文献
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B J Culliton 《Science (New York, N.Y.)》1988,242(4880):856-857
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Functional transfer of mitochondrial genes to the nucleus is very common in some taxa but entirely lacking in others. Current evolutionary theories to account for this variation predict that outcrossing, which allows escape from Muller's ratchet and faster spread of beneficial mutations, should favor gene transfer. We find that functional gene transfer is more common in selfing or clonal plants than in outcrossing plants, a pattern opposite to prediction. We suggest that reproductive modes, such as selfing and vegetative reproduction, conserve adaptive mitonuclear gene combinations, allowing functional transfer, whereas outcrossing prevents transfer by breaking up these combinations. 相似文献
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Purification and characterization of mouse hematopoietic stem cells 总被引:181,自引:0,他引:181
Mouse bone marrow hematopoietic stem cells were isolated with the use of a variety of phenotypic markers. These cells can proliferate and differentiate with approximately unit efficiency into myelomonocytic cells, B cells, or T cells. Thirty of these cells are sufficient to save 50 percent of lethally irradiated mice, and to reconstitute all blood cell types in the survivors. 相似文献