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Cell of Origin and Early Evolution of Leukemia in Down Syndrome

ABSTRACT: To investigate the mechanism by which GATA1s and STAG2 deficiency contribute to Down Syndrome leukemogenesis, specifically within the propagating CD34/CD117 cell fractions from primary xenografts, we carried out transcriptional and epigenetic profiling by RNAseq and ATACseq. The chromatin accessibility landscape was compared to bulk ATACseq of individually sorted N-FL HSPC subpopulations. To investigate the mechanism underlying the synergy between T21 and GATA1s in driving preleukemia development, we analyzed the binding occupancy of GATA1. We performed Cut&Run assays to profile genome-wide GATA1 binding sites and also to quantify binding changes upon GATA1s editing in N-FL and T21-FL CD34+ enriched HSPCs. Lastly, we profiled miRNAs from N-FL and T21-FL CD34+ enriched HSPCs by miRNA-Seq.

PROVIDER: EGAS00001004780 | EGA |

REPOSITORIES: EGA

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