Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells
dc.contributor.author | Yilmaz, O. H. | en_US |
dc.contributor.author | Valdez, Riccardo | en_US |
dc.contributor.author | Theisen, B. K. | en_US |
dc.contributor.author | Guo, W. | en_US |
dc.contributor.author | Ferguson, D. O. | en_US |
dc.contributor.author | Wu, Hong | en_US |
dc.contributor.author | Morrison, Sean J. | en_US |
dc.date.accessioned | 2009-06-01T17:21:25Z | |
dc.date.available | 2009-06-01T17:21:25Z | |
dc.date.issued | 2006-05-25 | en_US |
dc.identifier.citation | Yilmaz, OH; Valdez, R; Theisen, BK; Guo, W; Ferguson, DO; Wu, H; Morrison, SJ. (2006) "Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells." Nature 441(7092): 475-482. <http://hdl.handle.net/2027.42/62514> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62514 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16598206&dopt=citation | en_US |
dc.description.abstract | Recent advances have highlighted extensive phenotypic and functional similarities between normal stem cells and cancer stem cells. This raises the question of whether disease therapies can be developed that eliminate cancer stem cells without eliminating normal stem cells. Here we address this issue by conditionally deleting the Pten tumour suppressor gene in adult haematopoietic cells. This led to myeloproliferative disease within days and transplantable leukaemias within weeks. Pten deletion also promoted haematopoietic stem cell (HSC) proliferation. However, this led to HSC depletion via a cell-autonomous mechanism, preventing these cells from stably reconstituting irradiated mice. In contrast to leukaemia-initiating cells, HSCs were therefore unable to maintain themselves without Pten. These effects were mostly mediated by mTOR as they were inhibited by rapamycin. Rapamycin not only depleted leukaemia-initiating cells but also restored normal HSC function. Mechanistic differences between normal stem cells and cancer stem cells can thus be targeted to deplete cancer stem cells without damaging normal stem cells. | en_US |
dc.format.extent | 1013116 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Nature Publishing Group | en_US |
dc.source | Nature | en_US |
dc.title | Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Inst Life Sci, Dept Internal Med, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationother | Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA | en_US |
dc.identifier.pmid | 16598206 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62514/1/nature04703.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/nature04703 | en_US |
dc.identifier.source | Nature | en_US |
dc.contributor.authoremail | seanjm@umich.edu | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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