Similar Datasets
Project description:Ecotropic viral integration site 1 (EVI1/MECOM) overexpression is common in myeloid malignancies. We present a new Evi1 transgenic mouse model with inducible expression in hematopoietic stem cells (HSCs) and progenitor cells (HPCs) at lower levels. Upon exogenous Evi1 induction, mice displayed anemia, thrombocytopenia, lymphopenia, and dysplasia in erythroid and megakaryocyte cells with a significant expansion of committed myeloid progenitor cells, resembling human Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN)-like disease. Methods: LSK cells were sorted by Sony SH800 from 3 pairs of mice transplanted with WT BM cells and Evi1-OE BM cells after pIpC injection. Around 5X103 LSK cells were harvested from each mouse. Then the cells were lysated by Trizol and total RNA was extracted by phenol-chloroform. Results: Molecular pathways altered in LSK cells from recipient mice transplanted with Evi1-OE BM cells. Conclusions: Transcription profile changed in Evi1 overexpressing hematopoietic stem and progenitor cells.
2023-06-27 | GSE235441 | GEO
Project description:Ecotropic viral integration site 1 (EVI1/MECOM) overexpression is common in myeloid malignancies. We present a new Evi1 transgenic mouse model with inducible expression in hematopoietic stem cells (HSCs) and progenitor cells (HPCs) at lower levels. Upon exogenous Evi1 induction, mice displayed anemia, thrombocytopenia, lymphopenia, and dysplasia in erythroid and megakaryocyte cells with a significant expansion of committed myeloid progenitor cells, resembling human Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN)-like disease. Methods: Lin-C-Kit+ cells were isolated from 3 pairs of WT and Evi1 overexpressing mice. Around 1X106 Lin-C-Kit+ cells were harvested from each mouse. Then the cells were lysated by Trizol and total RNA was extracted by phenol-chloroform. Results: Molecular pathways altered in Lin-C-Kit+ cells from Evi1-OE mice. Conclusions: Multiple molecular pathways changed in Evi1 overexpressing hematopoietic stem and progenitor cells.
2023-06-27 | GSE235440 | GEO
Project description:Ecotropic viral integration site 1 (EVI1/MECOM) overexpression is common in myeloid malignancies. We present a new Evi1 transgenic mouse model with inducible expression in hematopoietic stem cells (HSCs) and progenitor cells (HPCs) at lower levels. Upon exogenous Evi1 induction, mice displayed anemia, thrombocytopenia, lymphopenia, and dysplasia in erythroid and megakaryocyte cells with a significant expansion of committed myeloid progenitor cells, resembling human Myelodysplastic syndrome/Myeloproliferative neoplasm (MDS/MPN)-like disease. Methods: Lin-C-Kit+ cells were isolated from 2 Evi1 overexpressing mice for CUT&RUN assay using flag antibody and IgG. Lin-C-Kit+ cells were isolated from 2 pair of WT mice and Evi1 overexpressing mice for CUT&RUN assay using H3K27me3 antibody.Around 5X105 Lin-C-Kit+ cells for each group were used in CUT&RUN assay. About 10 ng of the purified CUT&RUN DNA was used for preparation of multiplexed libraries with the NEB Ultra II DNA Library Prep Kit per manufacturer's instruction (NEB #E7103). Sequencing was conducted using an Illumina NextSeq 500 Sequencing System. Results: Molecular pathways altered in Lin-C-Kit+ cells from Evi1-OE mice. Conclusions: Evi1 has a special binding profiling in Lin-C-Kit+ cells. The modification profile of H3K27me3 was altered in Evi1-OE hematopoietic stem and progenitor cells.
2023-06-27 | GSE235439 | GEO
Project description:Evi1 governs Kdm6b-mediated histone demethylation to finely regulate the Laptm4b-driven mTORC pathway in vivo
| PRJNA986072 | ENA
Project description:Evi1 governs Kdm6b-mediated histone demethylation to finely regulate the Laptm4b-driven mTORC pathway in vivo [LK]
| PRJNA986078 | ENA
Project description:Evi1 governs Kdm6b-mediated histone demethylation to finely regulate the Laptm4b-driven mTORC pathway in vivo [LSK]
| PRJNA986077 | ENA
Project description:Evi1 governs Kdm6b-mediated histone demethylation to finely regulate the Laptm4b-driven mTORC pathway in vivo [CUT&RUN]
| PRJNA986076 | ENA
Project description:Rationale: Osteosarcoma (OS), the most common type of bone tumor, which seriously affects the patients' limb function and life quality. OS has a strong tendency of lung metastasis, and the five-year survival rate of patients with metastatic osteosarcoma is less than 20%. Thus, new treatment targets and strategies are urgently needed. Methods: The expression of the histone demethylase KDM6B and H3K27me3 levels in OS specimens were analyzed using quantitative PCR and immunohistochemical assays. The biological functions of KDM6B were determined using in vitro transwell, wound healing assays, and an in vivo orthotopic injection-induced lung metastasis model. Subsequently, chromatin immunoprecipitation sequencing (ChIP-seq) combined with transcriptomic RNA sequencing (RNA-seq), and subsequent ChIP-qPCR, western blot, and aerobic glycolysis assays were used to explore the mechanism of KDM6B function and validate the candidate target gene of KDM6B. Results: KDM6B expression was significantly upregulated in OS patients, and high KDM6B expression was associated with poorer prognosis in OS patients. Targeting KDM6B significantly inhibited OS cell migration in vitro and lung metastasis in vivo. RNA-seq and ChIP-seq analysis revealed that KDM6B increases lactate dehydrogenase LDHA expression in OS cells by directly mediating H3K27me3 demethylation. The phenotypes of inhibited cell metastasis in KDM6B-knockdown OS cells was reversed upon overexpression of LDHA. Finally, a small molecule inhibitor targeting KDM6B significantly inhibited OS cell migration in vitro and lung metastasis in vivo. Conclusions: Collectively, we elucidated that upregulated KDM6B facilitates tumor metastasis in OS via modulating LDHA expression. Our findings deepen the recognition of OS metastasis mechanism and suggest that KDM6B might be a new potential therapeutic target for the treatment of OS (especially highly metastatic OS).
| S-EPMC7914357 | biostudies-literature
Project description:Dermal Fibroblast Progenitors (DFPs) differentiate into distinct fibroblast lineages during skin development. However, the epigenetic mechanisms that regulate DFP differentiation are not known. Our objective was to use multimodal single-cell approaches, epigenetic assays, and allografting techniques to define a DFP state and the mechanism that governs its differentiation potential. Our initial results indicated that the overall transcription profile of DFPs is repressed by H3K27me3 and has inaccessible chromatin at lineage-specific genes. Surprisingly, the repressive chromatin profile of DFPs renders them unable to reform the skin in allograft assays despite their multipotent potential. We hypothesized that chromatin derepression was modulated by the H3K27me3 demethylase, Kdm6b/Jmjd3. Dermal fibroblast-specific deletion of Kdm6b/Jmjd3 in mice resulted in adipocyte compartment ablation and inhibition of mature dermal papilla functions, confirmed by additional single-cell RNA-seq, ChIP-seq, and allografting assays. We conclude that DFPs are functionally derepressed during murine skin development by Kdm6b/Jmjd3. Our studies therefore reveal a multimodal understanding of how DFPs differentiate into distinct fibroblast lineages and provide a novel publicly available multiomics search tool.
| S-EPMC10548174 | biostudies-literature
Project description:Dermal Fibroblast Progenitors (DFPs) differentiate into distinct fibroblast lineages during skin development. However, the epigenetic mechanisms that regulate DFP differentiation is not known. Our objective was to use multimodal single-cell approaches, epigenetic assays, and allografting techniques to define DFP state and the mechanism that governs its differentiation potential. Our initial results indicated that the overall transcription profile of DFPs is repressed by H3K27me3 and has inaccessible chromatin at lineage specific genes. Surprisingly, the repressive chromatin profile of DFPs renders them unable to reform skin in allograft assays despite their multipotent potential. We hypothesized that chromatin de-repression was modulated by the H3K27me3 demethylase, Kdm6b/Jmjd3. Dermal fibroblast-specific deletion of Kdm6b/Jmjd3 in mice resulted in adipocyte compartment ablation and inhibition of mature dermal papilla functions, confirmed by additional single cell RNA-seq, ChIP-seq, and allografting assays. We conclude that DFPs are functionally de-repressed during murine skin development by Kdm6b/Jmjd3. Our studies therefore reveal a multimodal understanding of how DFPs differentiate into distinct fibroblast lineages, and provide a novel publicly-available multiomics search-tool.
| S-SCDT-10_15252-EMBJ_2023113880 | biostudies-other