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Generation of a functional mammary gland from a single stem cell 总被引:1,自引:0,他引:1
Shackleton M Vaillant F Simpson KJ Stingl J Smyth GK Asselin-Labat ML Wu L Lindeman GJ Visvader JE 《Nature》2006,439(7072):84-88
The existence of mammary stem cells (MaSCs) has been postulated from evidence that the mammary gland can be regenerated by transplantation of epithelial fragments in mice. Interest in MaSCs has been further stimulated by their potential role in breast tumorigenesis. However, the identity and purification of MaSCs has proved elusive owing to the lack of defined markers. We isolated discrete populations of mouse mammary cells on the basis of cell-surface markers and identified a subpopulation (Lin-CD29hiCD24+) that is highly enriched for MaSCs by transplantation. Here we show that a single cell, marked with a LacZ transgene, can reconstitute a complete mammary gland in vivo. The transplanted cell contributed to both the luminal and myoepithelial lineages and generated functional lobuloalveolar units during pregnancy. The self-renewing capacity of these cells was demonstrated by serial transplantation of clonal outgrowths. In support of a potential role for MaSCs in breast cancer, the stem-cell-enriched subpopulation was expanded in premalignant mammary tissue from MMTV-wnt-1 mice and contained a higher number of MaSCs. Our data establish that single cells within the Lin-CD29hiCD24+ population are multipotent and self-renewing, properties that define them as MaSCs. 相似文献
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Mumby PJ Edwards AJ Arias-González JE Lindeman KC Blackwell PG Gall A Gorczynska MI Harborne AR Pescod CL Renken H Wabnitz CC Llewellyn G 《Nature》2004,427(6974):533-536
Mangrove forests are one of the world's most threatened tropical ecosystems with global loss exceeding 35% (ref. 1). Juvenile coral reef fish often inhabit mangroves, but the importance of these nurseries to reef fish population dynamics has not been quantified. Indeed, mangroves might be expected to have negligible influence on reef fish communities: juvenile fish can inhabit alternative habitats and fish populations may be regulated by other limiting factors such as larval supply or fishing. Here we show that mangroves are unexpectedly important, serving as an intermediate nursery habitat that may increase the survivorship of young fish. Mangroves in the Caribbean strongly influence the community structure of fish on neighbouring coral reefs. In addition, the biomass of several commercially important species is more than doubled when adult habitat is connected to mangroves. The largest herbivorous fish in the Atlantic, Scarus guacamaia, has a functional dependency on mangroves and has suffered local extinction after mangrove removal. Current rates of mangrove deforestation are likely to have severe deleterious consequences for the ecosystem function, fisheries productivity and resilience of reefs. Conservation efforts should protect connected corridors of mangroves, seagrass beds and coral reefs. 相似文献
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LKB1 modulates lung cancer differentiation and metastasis 总被引:1,自引:0,他引:1
Ji H Ramsey MR Hayes DN Fan C McNamara K Kozlowski P Torrice C Wu MC Shimamura T Perera SA Liang MC Cai D Naumov GN Bao L Contreras CM Li D Chen L Krishnamurthy J Koivunen J Chirieac LR Padera RF Bronson RT Lindeman NI Christiani DC Lin X Shapiro GI Jänne PA Johnson BE Meyerson M Kwiatkowski DJ Castrillon DH Bardeesy N Sharpless NE Wong KK 《Nature》2007,448(7155):807-810
Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis. 相似文献
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Roscioli T Cliffe ST Bloch DB Bell CG Mullan G Taylor PJ Sarris M Wang J Donald JA Kirk EP Ziegler JB Salzer U McDonald GB Wong M Lindeman R Buckley MF 《Nature genetics》2006,38(6):620-622
We describe mutations in the PML nuclear body protein Sp110 in the syndrome veno-occlusive disease with immunodeficiency, an autosomal recessive disorder of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease. This is the first report of the involvement of a nuclear body protein in a human primary immunodeficiency and of high-penetrance genetic mutations in hepatic veno-occlusive disease. 相似文献
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Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers 总被引:21,自引:0,他引:21
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Weir BA Woo MS Getz G Perner S Ding L Beroukhim R Lin WM Province MA Kraja A Johnson LA Shah K Sato M Thomas RK Barletta JA Borecki IB Broderick S Chang AC Chiang DY Chirieac LR Cho J Fujii Y Gazdar AF Giordano T Greulich H Hanna M Johnson BE Kris MG Lash A Lin L Lindeman N Mardis ER McPherson JD Minna JD Morgan MB Nadel M Orringer MB Osborne JR Ozenberger B Ramos AH Robinson J Roth JA Rusch V Sasaki H Shepherd F Sougnez C Spitz MR Tsao MS Twomey D Verhaak RG Weinstock GM Wheeler DA Winckler W 《Nature》2007,450(7171):893-898
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