RNA-Regulatory Exosome Complex Confers Erythroid Progenitor Cell Survival and Activity In Vivo
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA841586 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19358561_1.fastq.gz | Fastqsanger.gz | |||
| SRR19358561_2.fastq.gz | Fastqsanger.gz | |||
| SRR19358562_1.fastq.gz | Fastqsanger.gz | |||
| SRR19358562_2.fastq.gz | Fastqsanger.gz | |||
| SRR19358563_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:The RNA exosome complex (EC) confers post-transcriptional regulation by processing and degrading RNAs in a context-dependent manner. Although the EC functions in diverse cell types, its contributions to stem and progenitor cell development have not been widely studied. Previously, we demonstrated that the transcriptional regulator of erythrocyte development GATA1 represses genes encoding EC subunits, and in vitro analyses implicated the EC in maintaining erythroid progenitors. EC loss promoted the transition of progenitors into differentiating erythroblasts. To determine if these mechanisms operate in vivo, we utilized a hematopoietic-specific Vav1-Cre mouse system to conditionally ablate Exosc3, encoding an EC structural subunit with a conserved RNA binding domain. Although Exosc3 fl/fl Cre+ embryos developed normally until E14.5, Exosc3 ablation was embryonic lethal, severely reduced erythro-myeloid progenitor activity and reduced immunophenotypic progenitors. Exosc3 ablation decreased Kit+ hematopoietic progenitors and the level of cell surface c-Kit. RNA-seq analysis of Exosc3-ablated BFU-E revealed elevated transcripts encoding pro-apoptotic factors, including BCL2 family members Bax, Puma and Noxa, the death receptor Fas, and p53 target genes. Exosc3-ablated BFU-E and CFU-E progenitors exhibited increased apoptosis. Although megakaryocyte-erythroid progenitor (MEP) levels were unaltered, they were functionally defective. We propose that the EC controls an ensemble of apoptosis-regulatory RNAs, thereby conferring erythroid progenitor survival and promoting developmental erythropoiesis in vivo.
2022-09-26 | GSE203607 | GEO
Project description:The RNA-regulatory exosome complex (EC) posttranscriptionally and cotranscriptionally processes and degrades RNAs in a context-dependent manner. Although the EC functions in diverse cell types, its contributions to stem and progenitor cell development are not well understood. Previously, we demonstrated that the transcriptional regulator of erythrocyte development, GATA1, represses EC subunit genes, and the EC maintains erythroid progenitors in vitro. To determine if this mechanism operates in vivo, we used the hematopoietic-specific Vav1-Cre and "conditional by inversion" mouse system to ablate Exosc3, encoding an EC structural subunit. Although Exosc3C/C Cre+ embryos developed normally until embryonic day 14.5, Exosc3 ablation was embryonic lethal and severely reduced erythromyeloid progenitor activity. RNA sequencing analysis of Exosc3-ablated burst-forming unit-erythroid revealed elevated transcripts encoding multiple proapoptotic factors, and the mutant erythroid progenitors exhibited increased apoptosis. We propose that the EC controls an ensemble of apoptosis-regulatory RNAs, thereby promoting erythroid progenitor survival and developmental erythropoiesis in vivo.
| S-EPMC9984454 | biostudies-literature
Project description:Exosc8 and Exosc9 are components of the exosome that establish a barricade to erythroid maturation. Here, we knocked down Exosc8 in fetal liver-derived erythroid progenitor cells to determine the cohort of Exosc8-regulated genes in erythroid cells.
2014-08-09 | GSE60136 | GEO
Project description:Exosc8 and Exosc9 are components of the exosome that establish a barricade to erythroid maturation. Here, we knocked down Exosc8 in fetal liver-derived erythroid progenitor cells to determine the cohort of Exosc8-regulated genes in erythroid cells. Freshly isolated fetal liver progenitor cells were infected with retrovirus expressing shRNA targeting either luciferase or Exosc8. Total RNA was isolated from these cells after 3 days ex-vivo culture, during which the cells underwent erythroid maturation.
2014-08-09 | E-GEOD-60136 | biostudies-arrayexpress
Project description:Impact on erythroid progenitor type on erythroid differntiation
| PRJNA515507 | ENA
Project description:SCL/TAL1, a tissue-specific transcription factor of the basic helix-loop-helix (bHLH) family, and c-Kit, a tyrosine kinase receptor, control hematopoietic stem cell survival and quiescence. Here we report that SCL and c-Kit signaling control a common gene expression signature, of which 19 genes are associated with apoptosis. In vivo, SCL levels are limiting for the clonal expansion of Kit+ multipotent and erythroid progenitors. In addition, increased SCL expression specifically enhances the sensitivity of multipotent and megakaryocyte/erythroid progenitors to Steel factor (KIT ligand), whilst a DNA binding mutant antagonizes KIT function and induces apoptosis in progenitors. We conclude that Scl operates downstream of Kit to support the survival of megakaryocyte/erythroid progenitors. Finally, higher SCL expression upregulates Kit in normal bone marrow cells and increases chimerism after bone marrow transplantation, indicating that Scl is also upstream of Kit. We conclude that Scl and Kit establish a positive feedback loop in multipotent and megakaryocyte/erythroid progenitors. c-Kit regulated genes were extrapolated from gene expression profiles of TF-1 erythroid progenitor cells (empty MSCV vector) stimulated with SF (Kit ligand), Epo or GM-CSF. Second, SCL-regulated genes were obtained by expressing a DNA binding-defective SCL mutant (DbSCL) and selecting genes that were differentially expressed in M-oM-^AM-^DbSCL cells versus control cells (MSCV) stimulated with the same cytokines.
2013-07-06 | E-GEOD-48557 | biostudies-arrayexpress
Project description:SCL/TAL1, a tissue-specific transcription factor of the basic helix-loop-helix (bHLH) family, and c-Kit, a tyrosine kinase receptor, control hematopoietic stem cell survival and quiescence. Here we report that SCL and c-Kit signaling control a common gene expression signature, of which 19 genes are associated with apoptosis. In vivo, SCL levels are limiting for the clonal expansion of Kit+ multipotent and erythroid progenitors. In addition, increased SCL expression specifically enhances the sensitivity of multipotent and megakaryocyte/erythroid progenitors to Steel factor (KIT ligand), whilst a DNA binding mutant antagonizes KIT function and induces apoptosis in progenitors. We conclude that Scl operates downstream of Kit to support the survival of megakaryocyte/erythroid progenitors. Finally, higher SCL expression upregulates Kit in normal bone marrow cells and increases chimerism after bone marrow transplantation, indicating that Scl is also upstream of Kit. We conclude that Scl and Kit establish a positive feedback loop in multipotent and megakaryocyte/erythroid progenitors.
2013-07-06 | GSE48557 | GEO
Project description:The exosome complex plays key roles in RNA processing and degradation in Eukaryotes and Archaea. Outstanding structural studies have identified multiple pathways for RNA substrates into the exosome complex in vitro, but determining which pathways are preferentially followed by individual RNA species in vivo remains challenging. Here we attempted to address this important question by an RNase protection approach. We applied an in vivo RNA-protein crosslinking technique to the exosome component Rrp44/Dis2, which has both endonuclease and exonuclease activity. The resulting high-throughput sequence reads were stratified by length of the cDNA. This should reflect the length of the RNA fragments, and therefore the RNA region that was protected by exosome binding. Striking effects were seen for short fragments, which presumably arise from RNA species that follow the “direct access” route to the Rrp44 exonuclease active site. These were strongly elevated in strains lacking exonuclease activity and, surprisingly, suppressed by point mutations in the endonuclease active site. This indicates that the short fragments are degraded by the exonuclease activity of Rrp44, but also suggest that they are generated by the endonuclease activity. Confident mapping of the short reads is challenging but it seems clear that they are derived from only a subset of exosome targets. In particular, pre-rRNA species, which are major exosome targets, are strongly disfavored for the generation of short reads.
2017-02-15 | GSE94889 | GEO
Project description:Cellular differentiation requires vast remodeling of transcriptomes, and therefore machinery mediating remodeling controls differentiation. Relative to transcriptional mechanisms governing differentiation, post-transcriptional processes are less well understood. As an important post-transcriptional determinant of transcriptomes, the RNA exosome complex (EC) mediates processing and/or degradation of select RNAs. During erythropoiesis, the erythroid transcription factor GATA1 represses EC subunit genes. Depleting EC structural subunits prior to GATA1-mediated repression is deleterious to erythroid progenitor cells. To assess the importance of the EC catalytic subunits Dis3 and Exosc10 in this dynamic process, we asked if these subunits function non-redundantly to control erythropoiesis. Dis3 or Exosc10 depletion in primary murine hematopoietic progenitor cells reduced erythroid progenitors and their progeny, while sparing myeloid cells. Dis3 loss severely compromised erythroid progenitor and erythroblast survival, rendered erythroblasts hypersensitive to apoptosis-inducing stimuli and induced γ-H2AX, indicative of DNA double-stranded breaks. Dis3 loss-of-function phenotypes were more severe than those caused by Exosc10 depletion. We innovated a genetic rescue system to compare human Dis3 with multiple myeloma-associated Dis3 mutants S447R and R750K, and only wild type Dis3 was competent to rescue progenitors. Thus, Dis3 establishes a disease mutation-sensitive, cell type-specific survival mechanism to enable a differentiation program.
| S-EPMC8450083 | biostudies-literature