GSE129691 Setd2 deficiency impaired erythroid differentiation and accelerated Myelodysplastic Syndrome(MDS) - associated leukemogenesis through S100A8 and S100A9

Contributors : Bingyi Chen ; Shubei Chen ; Chun-Hui Xu ; Xiao-Jian Sun ; Lan WangSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencing ; Methylation profiling by high throughput sequencingOrganism : Mus musculusSetd2, the histone H3 lysine 36 methyltransferase, plays an important role in the pathogenesis of hematologic malignancies. The research on the role of Setd2 in leukemogenesis has made great progress, but its role in MDS is still unknown. Here, we knock out Setd2 in the NUP98-HOXD13 transgenic (NHD13 Tg) mouse, and demonstrate that loss of Setd2 accelerates the transformation of MDS into AML. The conditional deletion of Setd2 also interferes the differentiation of hematopoietic stem and progenitor cells (HSPCs), and results in the decrease of granulocyte monocyte progenitor (GMP) cells, increase of megakaryocyte erythroid progenitor (MEP) cells and common myeloid progenitor (CMP) cells. Loss of Setd2 impairs erythroid differentiation, includes cell cycle arrest in G2-M and enhances the selt-renewal ability of HSPCS. Our RNA-seq,ChIP-seq and WGBS analysis indicats that S100A8 and S100A9 are direct target genes of H3K36me3 and expression of heterodimeric S100 calcium-binding proteins S100A8 and S100A9 are downregulated in HSPCs when Setd2 deficiency. Addition of recombinant S100A8 or S100A9 weakens the clonogenic progenitors of Setd2 deficient HSPCs. Therefore, our results demonstrate that...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Methylation profiling by high throughput sequencing Mus musculus Source Type: research