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dc.contributor.authorSaadatpour, Assiehen_US
dc.contributor.authorGuo, Guojien_US
dc.contributor.authorOrkin, Stuart Hen_US
dc.contributor.authorYuan, Guo-Chengen_US
dc.date.accessioned2015-01-05T18:27:58Z
dc.date.issued2014en_US
dc.identifier.citationSaadatpour, Assieh, Guoji Guo, Stuart H Orkin, and Guo-Cheng Yuan. 2014. “Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis.” Genome Biology 15 (12): 525. doi:10.1186/s13059-014-0525-9. http://dx.doi.org/10.1186/s13059-014-0525-9.en
dc.identifier.issn1465-6906en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13581185
dc.description.abstractBackground: A fundamental challenge for cancer therapy is that each tumor contains a highly heterogeneous cell population whose structure and mechanistic underpinnings remain incompletely understood. Recent advances in single-cell gene expression profiling have created new possibilities to characterize this heterogeneity and to dissect the potential intra-cancer cellular hierarchy. Results: Here, we apply single-cell analysis to systematically characterize the heterogeneity within leukemic cells using the MLL-AF9 driven mouse model of acute myeloid leukemia. We start with fluorescence-activated cell sorting analysis with seven surface markers, and extend by using a multiplexing quantitative polymerase chain reaction approach to assay the transcriptional profile of a panel of 175 carefully selected genes in leukemic cells at the single-cell level. By employing a set of computational tools we find striking heterogeneity within leukemic cells. Mapping to the normal hematopoietic cellular hierarchy identifies two distinct subtypes of leukemic cells; one similar to granulocyte/monocyte progenitors and the other to macrophage and dendritic cells. Further functional experiments suggest that these subtypes differ in proliferation rates and clonal phenotypes. Finally, co-expression network analysis reveals similarities as well as organizational differences between leukemia and normal granulocyte/monocyte progenitor networks. Conclusions: Overall, our single-cell analysis pinpoints previously uncharacterized heterogeneity within leukemic cells and provides new insights into the molecular signatures of acute myeloid leukemia. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0525-9) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s13059-014-0525-9en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262970/pdf/en
dash.licenseLAAen_US
dc.titleCharacterizing heterogeneity in leukemic cells using single-cell gene expression analysisen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalGenome Biologyen
dash.depositing.authorGuo, Guojien_US
dc.date.available2015-01-05T18:27:58Z
dc.identifier.doi10.1186/s13059-014-0525-9*
dash.contributor.affiliatedGuo, Guoji
dash.contributor.affiliatedOrkin, Stuart


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