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Embryonic stem cells offer unprecedented opportunities for random or targeted genome alterations in the mouse. We present here an efficient strategy to create chromosome-specific loss of heterozygosity in embryonic stem cells. The combination of this method with genome-wide mutagenesis in ES cells (using chemical mutagens or gene-trap vectors) opens up the possibility for in vitro or in vivo functional screening of recessive mutations in the mouse. 相似文献
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Identification of human brain tumour initiating cells 总被引:3,自引:0,他引:3
Singh SK Hawkins C Clarke ID Squire JA Bayani J Hide T Henkelman RM Cusimano MD Dirks PB 《Nature》2004,432(7015):396-401
The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10(5) CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies. 相似文献
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Perry JN Firbank LG Champion GT Clark SJ Heard MS May MJ Hawes C Squire GR Rothery P Woiwod IP Pidgeon JD 《Nature》2004,428(6980):313-316
The UK Farm-Scale Evaluations (FSE) compared the effects on biodiversity of management of genetically modified herbicide-tolerant (GMHT) spring-sown crops with conventional crop management. The FSE reported larger weed abundance under GMHT management for fodder maize, one of three crops studied. Increased seed production may be important for the long-term persistence of these arable weeds and may benefit invertebrates, small mammals and seed-eating birds. In three-quarters of FSE maize fields, growers used atrazine on the conventionally managed half, reflecting contemporary commercial practice. Withdrawal of the triazine herbicides atrazine, simazine and cyanazine from approved lists of EU chemicals could therefore reduce or even reverse the reported benefits of GMHT maize. Here we analyse effects of applications of triazine herbicides in conventional maize regimes on key indicators, using FSE data. Weed abundances were decreased greatly relative to all other regimes whenever atrazine was applied before weeds emerged. Here, we forecast weed abundances in post-triazine herbicide regimes. We predict weed abundances under future conventional herbicide management to be considerably larger than that for atrazine used before weeds emerged, but still smaller than for the four FSE sites analysed that used only non-triazine herbicides. Our overall conclusion is that the comparative benefits for arable biodiversity of GMHT maize cropping would be reduced, but not eliminated, by the withdrawal of triazines from conventional maize cropping. 相似文献
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J M Squire 《Nature》1971,233(5320):457-462
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Z Ma S W Morris V Valentine M Li J A Herbrick X Cui D Bouman Y Li P K Mehta D Nizetic Y Kaneko G C Chan L C Chan J Squire S W Scherer J K Hitzler 《Nature genetics》2001,28(3):220-221
t(1;22) is the principal translocation of acute megakaryoblastic leukemias. Here we show this chromosomal rearrangement to result in the fusion of two novel genes, RNA-binding motif protein-15 (RBM15), an RNA recognition motif-encoding gene with homology to Drosophila spen, and Megakaryoblastic Leukemia-1 (MKL1), a gene encoding an SAP (SAF-A/B, Acinus and PIAS) DNA-binding domain. 相似文献
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Memory for places learned long ago is intact after hippocampal damage. 总被引:11,自引:0,他引:11
The hippocampus is part of a system of structures in the medial temporal lobe that are essential for memory. One influential view of hippocampal function emphasizes its role in the acquisition and retrieval of spatial knowledge. By this view, the hippocampus constructs and stores spatial maps and is therefore essential for learning and remembering places, including those learned about long ago. We tested a profoundly amnesic patient (E.P.), who has virtually complete bilateral damage to the hippocampus and extensive damage to adjacent structures in the medial temporal lobe. We asked him to recall the spatial layout of the region where he grew up, from which he moved away more than 50 years ago. E.P. performed as well as or better than age-matched control subjects who grew up in the same region and also moved away. In contrast, E.P. has no knowledge of his current neighbourhood, to which he moved after he became amnesic. Our results show that the medial temporal lobe is not the permanent repository of spatial maps, and support the view that the hippocampus and other structures in the medial temporal lobe are essential for the formation of long-term declarative memories, both spatial and non-spatial, but not for the retrieval of very remote memories, either spatial or non-spatial. 相似文献
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