Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA348794 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aid is a key regulator of myeloid/erythroid differentiation and DNA methylation in murine hematopoietic stem/progenitor cells
| PRJNA348759 | ENA
Project description:Recent studies have uncovered that activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 in various myeloid malignancies and aberrant hematopoietic stem cell (HSC) self-renewal/differentiation in mice with hematopoietic tissue specific loss of Tet2 have been reported, indicating that TET2 is a master regulator of normal and malignant hematopoiesis. Despite a functional link between AID and TET in epigenetic gene regulation, the role of AID loss in normal hematopoiesis and myeloid transformation remains to be investigated. Here, we show that Aid loss in mice leads to expansion of myeloid cells and contraction in erythroid progenitors resulting in pathologic anemia possibly due to dysregulated expression of Cebpa and Gata1, myeloid/erythroid lineage specific transcription factors. Consistent with data in the murine context, silencing of AID skews differentiation towards myelomonocytic lineage in human BM cells. However, in contrast to Tet2, Aid loss does not contribute to enhanced HSC self-renewal or cooperate with Flt3-ITD in myeloid leukemogenesis. Genome-wide transcription and differential methylation analysis uncover critical role of Aid as a key epigenetic regulator. These results indicate that AID and TET2 share common effects on myeloid and erythroid lineage differentiation, and that their role is non-redundant in regulating HSC self-renewal and in myeloid transformation.
2017-10-01 | GSE88842 | GEO
Project description:Recent studies have uncovered that activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 in various myeloid malignancies and aberrant hematopoietic stem cell (HSC) self-renewal/differentiation in mice with hematopoietic tissue specific loss of Tet2 have been reported, indicating that TET2 is a master regulator of normal and malignant hematopoiesis. Despite a functional link between AID and TET in epigenetic gene regulation, the role of AID loss in normal hematopoiesis and myeloid transformation remains to be investigated. Here, we show that Aid loss in mice leads to expansion of myeloid cells and contraction in erythroid progenitors resulting in pathologic anemia possibly due to dysregulated expression of Cebpa and Gata1, myeloid/erythroid lineage specific transcription factors. Consistent with data in the murine context, silencing of AID skews differentiation towards myelomonocytic lineage in human BM cells. However, in contrast to Tet2, Aid loss does not contribute to enhanced HSC self-renewal or cooperate with Flt3-ITD in myeloid leukemogenesis. Genome-wide transcription and differential methylation analysis uncover critical role of Aid as a key epigenetic regulator. These results indicate that AID and TET2 share common effects on myeloid and erythroid lineage differentiation, and that their role is non-redundant in regulating HSC self-renewal and in myeloid transformation.
2017-10-01 | GSE88841 | GEO
Project description:Aid is a key regulator of myeloid/erythroid differentiation and DNA methylation in murine hematopoietic stem/progenitor cells (RNA-Seq)
| PRJNA348793 | ENA
Project description:Master hematopoietic transcription factors and long non-coding RNAs (lncRNAs) coordinate shaping lineage-restricted gene expression programs during hematopoietic differentiation. The architectural protein CCCTC-binding factor (CTCF) has emerged as an important regulator of gene expression in cell differentiation. However, the relationship and its regulatory effect on lncRNA genes in hematopoiesis remains elusive. We demonstrated that CTCF constrains DUBR transcription throughout erythroid differentiation, which was highly expressed in human hematopoietic stem and progenitor cells (HSPC) but depleted in erythroblasts. DUBR depletion enhances the expression of myeloid-erythroid cell differentiation genes by coordinating genome-wide enhancer activation and reducing the activity of the transcriptional repressor HES1 at gene promoters. Our results indicate that CTCF prevents DUBR transcription to coordinate a myeloid-erythroid gene expression program.
2024-05-28 | GSE268502 | GEO
Project description:Master hematopoietic transcription factors and long non-coding RNAs (lncRNAs) coordinate shaping lineage-restricted gene expression programs during hematopoietic differentiation. The architectural protein CCCTC-binding factor (CTCF) has emerged as an important regulator of gene expression in cell differentiation. However, the relationship and its regulatory effect on lncRNA genes in hematopoiesis remains elusive. We demonstrated that CTCF constrains DUBR transcription throughout erythroid differentiation, which was highly expressed in human hematopoietic stem and progenitor cells (HSPC) but depleted in erythroblasts. DUBR depletion enhances the expression of myeloid-erythroid cell differentiation genes by coordinating genome-wide enhancer activation and reducing the activity of the transcriptional repressor HES1 at gene promoters. Our results indicate that CTCF prevents DUBR transcription to coordinate a myeloid-erythroid gene expression program.
2024-05-28 | GSE268501 | GEO
Project description:Master hematopoietic transcription factors and long non-coding RNAs (lncRNAs) coordinate shaping lineage-restricted gene expression programs during hematopoietic differentiation. The architectural protein CCCTC-binding factor (CTCF) has emerged as an important regulator of gene expression in cell differentiation. However, the relationship and its regulatory effect on lncRNA genes in hematopoiesis remains elusive. We demonstrated that CTCF constrains DUBR transcription throughout erythroid differentiation, which was highly expressed in human hematopoietic stem and progenitor cells (HSPC) but depleted in erythroblasts. DUBR depletion enhances the expression of myeloid-erythroid cell differentiation genes by coordinating genome-wide enhancer activation and reducing the activity of the transcriptional repressor HES1 at gene promoters. Our results indicate that CTCF prevents DUBR transcription to coordinate a myeloid-erythroid gene expression program.
2024-05-28 | GSE268500 | GEO
Project description:To better understand the early events regulating lineage-specific hematopoietic differentiation, we analyzed the transcriptional profiles of CD34+ human hematopoietic stem and progenitor cells (HSPCs) subjected to differentiation stimulus. CD34+ cells were cultured for 12 and 40 hours in liquid cultures with supplemented media favoring myeloid or erythroid commitment. Serial analysis of gene expression (SAGE) was employed to generate four independent libraries. CD34+ Hematopoietic Stem Progenitor Cells with no differentiation stimulus were used as a control library.
2010-12-01 | E-GEOD-22092 | biostudies-arrayexpress
Project description:Myelodysplastic syndromes (MDS) are a group of hematologic neoplasms in which the bone marrow fails to produce enough mature blood cells, leading to peripheral blood cytopenias and myeloproliferation1-3. The average survival time following diagnosis of MDS is 2.5 years4, owing to few treatment options5. Roughly 20-30% of MDS patients progress to acute myeloid leukemia6. Risks of allogeneic bone marrow transplants in elderly patients, together with a dearth of effective FDA-approved drugs, make it imperative to revisit the origins of hematopoietic differentiation defects underlying MDS to identify new druggable targets7-9. We recently reported that haploinsufficiency of the atypical kinase Riok2 (Right open reading frame kinase 2)10 in mice leads to anemia and MDS-associated phenotypes11. However, the underlying molecular mechanisms remain largely unexplored. Here we show that RIOK2 is a master transcription factor that not only drives erythroid lineage commitment, but simultaneously suppresses megakaryocytic and myeloid lineages in primary human stem and progenitor cells. Structural modeling, chromatin immunoprecipitation sequencing, ATAC-sequencing and structure-function domain deletion mutants revealed that RIOK2 activates or represses specific genetic programs in hematopoiesis via its previously unappreciated winged helix-turn-helix DNA-binding domain and two transactivation domains. Mechanistically, RIOK2 functions as a master regulator of hematopoietic lineage commitment by controlling the expression of key lineage-specific transcription factors, such as GATA1, GATA2, SPI1, RUNX3 and KLF1. We also show that GATA1 and RIOK2 function in a positive feedback loop to drive erythroid differentiation. These discoveries present novel therapeutic opportunities to correct hematopoietic differentiation defects in MDS, in the anemia of chronic diseases such as renal failure and inflammation, and in other bone marrow failure disorders.
2021-10-16 | MSV000088238 | MassIVE
Project description:Erythroid differentiation-associated gene (EDAG), a hematopoietic tissue-specific transcription regulator, plays a key role in maintaining the homeostasis of hematopoietic lineage commitment. However, the mechanism and genes regulated by EDAG remain unknown.Here, we performed genome-wide parallel expression analyses of 32D cells stably transfected with EDAG. Total RNA from the control 32D cells and 32D/EDAG cells were used to generate target cDNA, and then hybridized to 36k Mouse Genome Array Genechips, representing about 25000 characterized murine genes.
2010-07-01 | E-GEOD-18862 | biostudies-arrayexpress