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Stingl J Eirew P Ricketson I Shackleton M Vaillant F Choi D Li HI Eaves CJ 《Nature》2006,439(7079):993-997
Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer. Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem cell with self-renewal potential. However, analysis of the properties and regulation of mammary stem cells has been limited by a lack of methods for their prospective isolation. Here we report the use of multi-parameter cell sorting and limiting dilution transplant analysis to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions. These mammary stem cells are phenotypically distinct from and give rise to mammary epithelial progenitor cells that produce adherent colonies in vitro. The mammary stem cells are also a rapidly cycling population in the normal adult and have molecular features indicative of a basal position in the mammary epithelium. 相似文献
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J M Diamond 《Nature》1999,400(6740):120-121
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Inoue K Khajavi M Ohyama T Hirabayashi S Wilson J Reggin JD Mancias P Butler IJ Wilkinson MF Wegner M Lupski JR 《Nature genetics》2004,36(4):361-369
The molecular mechanisms by which different mutations in the same gene can result in distinct disease phenotypes remain largely unknown. Truncating mutations of SOX10 cause either a complex neurocristopathy designated PCWH or a more restricted phenotype known as Waardenburg-Shah syndrome (WS4; OMIM 277580). Here we report that although all nonsense and frameshift mutations that cause premature termination of translation generate truncated SOX10 proteins with potent dominant-negative activity, the more severe disease phenotype, PCWH, is realized only when the mutant mRNAs escape the nonsense-mediated decay (NMD) pathway. We observe similar results for truncating mutations of MPZ that convey distinct myelinopathies. Our experiments show that triggering NMD and escaping NMD may cause distinct neurological phenotypes. 相似文献
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Ferguson IB 《浙江大学学报(自然科学英文版)》2004,5(2):129-132
Like animals, plants have evolved to survive in almost every climatic and environmental niche available. They have, however, evolved more sophisticated and varied methods to enable them to survive environmental changes in light, temperature, atmosphere composition, water and nutrients and 相似文献