ABSTRACT: Gene expression changes induced by BAY1436032 (IDH1mut inhibitor) in sorted human (CD45+) cells from bone marrow of IDH1mut patient derived xenotransplantation mice model
Project description:Gene expression changes induced by hypomethylating agent, Azacitidine (AZA) IDH1 inhibitor, BAY1436032 (BAY) and combination of BAY and AZA in sorted human (CD45+) cells from bone marrow of IDH1mut Patient derived Xenotransplantation mice model.
Project description:RNA and ATAC sequencing data of primary sorting CD45-Ter119-CD31-Scf; GFP+Cxcl12; DsRed+ bone marrow stromal cells ,2D cultured bone marrow stromal cells and 3D cultured bone marrow stromal cells. RNA sequencing data of sorted primary and 3D cocultured Lin-Sca1+C-kit+CD150+CD48+ hematopoietic stem cells from 8-12 weeks and 12-13 months old mice. RNA and ATAC sequencing data of primary sorting CD45-Ter119-CD31-Pdgfra+td-Tomato+ bone marrow stromal cells from young (8 wks), middle aged (12 months) and aged (22-24 months) Lepr-Cre;td-Tomato mice.
Project description:Mutations in the enzymes IDH1 and IDH2 have been identified in a wide variety of tumors like glioma, chondrosarcoma, thyroid cancer, lymphoma, melanoma, and in acute myeloid leukemia. Mutated IDH1/2 produces the metabolite 2-hydroxyglutarate (2HG), which interferes with epigenetic regulation of gene expression, and thus may promote tumorigenesis. HoxA9 immortalized bone marrow cells from C57BJ/6 mice were transduced with either empty vector or pSF91-IDH1wt-IRES-EGFP, or pSF91-IDH1mut-IRES-GFP and transplanted in irradiated recipient mice. Four weeks after transplantation, GFP+ cells were sorted from mouse bone marrow, from which total RNA was extracted and subjected to microarray analysis.
Project description:Purpose: To identify the mechanistic changes that lead to impaired osteogenesis and spontaneous osteoclast formation in both the hematopoietic and mesenchymal cell populations the makeup bone marrow cultures derived from cherubism mice (Sh3bp2KI/KI). Methods: Bone marrow cultures derived from wild type and cherubism mice were grown for seven days. On day seven, hematopoietic and mesenchymal cell types were sorted using CD45 and Sca1 cell surface markers. CD45+Sca1+ identified the hematopoietic population. CD45-Sca1+ identified the mesenchymal population. Total RNA was prepared from cell sorted populations. RNA quality was confirmed, ribosomal RNAs were depleted, libraries were prepared, and paired-end sequencing was performed on a illumina platform. We performed this study using six biological replicates. Results: Gene expression differences were identified Conclusions: Our study, for the first time, identifies the impact of a cherubism mutation on the global transcriptome of hematopoietic and mesenchymal cells extracted from murine bone marrow stromal cultures. With this study, we have found novel molecular signatures that are consistent with the cherubism phenotype (inflammation, bone loss, and fibrosis).
Project description:Mutations in the enzymes IDH1 and IDH2 have been identified in a wide variety of tumors like glioma, chondrosarcoma, thyroid cancer, lymphoma, melanoma, and in acute myeloid leukemia. Mutated IDH1/2 produces the metabolite 2-hydroxyglutarate (2HG), which interferes with epigenetic regulation of gene expression, and thus may promote tumorigenesis. HoxA9 immortalised bone marrow cells from C57BJ/6 mice were tranduced with either empty vector or pSF91-IDH1wt-IRES-EGFP, or pSF91-IDH1mut-IRES-GFP and transplanted in irradiated recipient mice. Alternatively, HoxA9 immortalised cells transduced with empty vector transplanted mice were treated with R-2HG at dose of 1mg/day for four weeks. Four weeks after transplantation/treatment GFP+ cells were sorted from mouse bone marrow, from which total RNA ws extracted and subjected to microarray analysis.
Project description:CD138 sorted bone marrow plasma cell were obtained from a normal patient, a multiple myelow with slow proliferation and a multiple myelow with rapid proliferation.
