Tracking epigenetic changes during human leukemogenesis
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ABSTRACT:
PROVIDER: PRJNA597528 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic changes in Down syndrome leukemogenesis
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Project description:We have developed a human model leukemia system where healthy cord blood (CB) cells from single donors are used to generate dozens of human leukemias driven by KMT2A fusions. These models have been used for the study of the stepwise changes in donor CB cells as they undergo leukemic transformation driven by the KMT2A-MLLT3 (KM3) fusion gene. We specifically studied the epigenetic changes that occur in this specific AML subgroup through ChIP-seq of histone modifications and ATAC-seq and DNA methylation through Methyl-Seq.
2020-07-01 | GSE142579 | GEO
Project description:Tracking of epigenetic changes during hematopoietic differentiation of induced pluripotent stem cells
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Project description:Acute megakaryoblastic leukemia (AMKL) is more frequently seen in Down syndrome patients, where it is often preceded by a transient myeloproliferative disorder (DS-TMD). The development of DS-TMD and DS-AMKL require not only the presence of the trisomy 21 but also that of GATA1 mutations. However, despite extensive studies into the genetics of DS-AMKL, not much is known about the epigenetic deregulation associated with this disease. In order to understand how epigenetic changes at the DNA methylation level contribute to DS leukemogenesis we performed DNA methylation profiling at different stages of development of this disease and analyzed the dynamics of epigenetic reprogramming. Early genome-wide epigenetic changes can be detected in trisomy 21 fetal liver mononuclear cells, even prior to the development of hematological abnormalities. These early changes are characterized by marked loss of DNA methylation at genes associated with regulation of key developmental processes. This first wave of aberrant DNA hypomethylation is followed by a second wave of epigenetic reprogramming detected in blast cells from DS-TMD and DS-AMKL, characterized by gains of methylation. This second wave of hypermethylation targets a distinct set of genes, preferentially affecting genes involved in hematopoiesis and regulation of cell growth and proliferation. DNA methylation profiles obtained at different stages of the development of Down syndrome AMKL and from CD41+ cells from partial trisomic mice
2013-08-19 | E-GEOD-46167 | biostudies-arrayexpress
Project description:Epigenetic enhancer changes during oncogenic transformation
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Project description:Acute megakaryoblastic leukemia (AMKL) is more frequently seen in Down syndrome patients, where it is often preceded by a transient myeloproliferative disorder (DS-TMD). The development of DS-TMD and DS-AMKL require not only the presence of the trisomy 21 but also that of GATA1 mutations. However, despite extensive studies into the genetics of DS-AMKL, not much is known about the epigenetic deregulation associated with this disease. In order to understand how epigenetic changes at the DNA methylation level contribute to DS leukemogenesis we performed DNA methylation profiling at different stages of development of this disease and analyzed the dynamics of epigenetic reprogramming. Early genome-wide epigenetic changes can be detected in trisomy 21 fetal liver mononuclear cells, even prior to the development of hematological abnormalities. These early changes are characterized by marked loss of DNA methylation at genes associated with regulation of key developmental processes. This first wave of aberrant DNA hypomethylation is followed by a second wave of epigenetic reprogramming detected in blast cells from DS-TMD and DS-AMKL, characterized by gains of methylation. This second wave of hypermethylation targets a distinct set of genes, preferentially affecting genes involved in hematopoiesis and regulation of cell growth and proliferation.
2013-08-19 | GSE46167 | GEO
Project description:Tracking Epigenetic Modification-Mediated Genome Organization
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Project description:Epigenetic changes during long term intestinal organoid culture
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Project description:Tracking transcriptional changes in a species-specific manner during experimental hepatoblastoma progression in vivo
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Project description:Differentiation of induced pluripotent stem cells (iPSCs) toward hematopoietic progenitor cells (HPCs) raises high hopes for disease modelling, drug screening, and cellular therapy. Various differentiation protocols have been established to generate iPSC-derived HPCs (iHPCs) that resemble their primary counterparts in morphology and immunophenotype, whereas a systematic epigenetic comparison was yet elusive. In this study, we compared genome wide DNA methylation (DNAm) patterns of iHPCs with various different hematopoietic subsets. Furthermore, we analyzed if additional co-culture for two weeks with syngenic primary mesenchymal stromal cells (MSCs) or iPSC-derived MSCs (iMSCs) further supports epigenetic maturation toward hematopoietic lineage. After 20 days of in vitro differentiation cells revealed typical hematopoietic morphology, CD45 expression and colony forming unit (CFU) potential. DNAm changes were particularly observed in genes that are associated with hematopoietic differentiation. On the other hand, the epigenetic profiles of iHPCs remained overall very distinct from normal hematopoiesis. Co-culture with MSCs or iMSCs enhanced proliferation of iHPCs and maintenance of CFU potential. However, morphology, immunophenotype, and DNAm profiles did not indicate that additional culture expansion with stromal support increases hematopoietic differentiation. In conclusion, differentiation of iPSCs towards hematopoietic lineage remains epigenetically incomplete. These results substantiate the need to elaborate advanced differentiation regimen while DNAm profiles provide a suitable measure to track this process.
2019-01-24 | GSE119079 | GEO