Tweet
Syndicated from PubMed RSS Feeds
RNA-seq analysis of two closely related leukemia clones that differ in their self-renewal capacity.
Blood. 2010 Oct 27;
Authors: Wilhelm BT, Briau M, Austin P, Faubert A, Boucher G, Chagnon P, Hope K, Girard S, Mayotte N, Landry JR, Hébert J, Sauvageau G
The molecular mechanisms regulating self-renewal of leukemia stem cells remain poorly understood. Here we report the generation of two closely related leukemias created through the retroviral over expression of Meis1 and Hoxa9. Despite their apparent common origin, these clonal leukemias exhibit enormous differences in stem cell frequency (from 1 in 1.4 (FLA2) to 1 in 347 (FLB1)), suggesting that one of these leukemias undergoes nearly unlimited self-renewal divisions. Using next-generation RNA sequencing, we characterized the transcriptomes of these phenotypically similar, but biologically distinct, leukemias, identifying hundreds of differentially expressed genes and a large number of structural differences (e.g. alternative splicing and promoter usage). Focusing on ligand-receptor pairs, we observed high expression levels of Sdf1-Cxcr4; Jagged2-Notch2/1; Osm-Gp130; Scf-cKit and Bmp15-Tgfb1/2. Interestingly, the integrin beta 2-like gene (Itgb2l) is both highly expressed and differentially expressed between our 2 leukemias (~14X higher in FLA2 than FLB1). Additionally, gene ontology analysis indicated GPCR receptors had a much higher proportion of differential expression (22%) compared to other classes (~5%) suggesting a potential role regulating subtle changes in cellular behavior. These results provide the first comprehensive transcriptome analysis of a leukemia stem cell and document an unexpected level of transcriptome variation between phenotypically similar leukemic cells.
PMID: 20980679 [PubMed - as supplied by publisher]
More...
RNA-seq analysis of two closely related leukemia clones that differ in their self-renewal capacity.
Blood. 2010 Oct 27;
Authors: Wilhelm BT, Briau M, Austin P, Faubert A, Boucher G, Chagnon P, Hope K, Girard S, Mayotte N, Landry JR, Hébert J, Sauvageau G
The molecular mechanisms regulating self-renewal of leukemia stem cells remain poorly understood. Here we report the generation of two closely related leukemias created through the retroviral over expression of Meis1 and Hoxa9. Despite their apparent common origin, these clonal leukemias exhibit enormous differences in stem cell frequency (from 1 in 1.4 (FLA2) to 1 in 347 (FLB1)), suggesting that one of these leukemias undergoes nearly unlimited self-renewal divisions. Using next-generation RNA sequencing, we characterized the transcriptomes of these phenotypically similar, but biologically distinct, leukemias, identifying hundreds of differentially expressed genes and a large number of structural differences (e.g. alternative splicing and promoter usage). Focusing on ligand-receptor pairs, we observed high expression levels of Sdf1-Cxcr4; Jagged2-Notch2/1; Osm-Gp130; Scf-cKit and Bmp15-Tgfb1/2. Interestingly, the integrin beta 2-like gene (Itgb2l) is both highly expressed and differentially expressed between our 2 leukemias (~14X higher in FLA2 than FLB1). Additionally, gene ontology analysis indicated GPCR receptors had a much higher proportion of differential expression (22%) compared to other classes (~5%) suggesting a potential role regulating subtle changes in cellular behavior. These results provide the first comprehensive transcriptome analysis of a leukemia stem cell and document an unexpected level of transcriptome variation between phenotypically similar leukemic cells.
PMID: 20980679 [PubMed - as supplied by publisher]
More...