Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA149081 | ENA |
REPOSITORIES: ENA
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Project description:The transcription factor Runx1 is essential for the establishment of definitive hematopoiesis during embryonic development. In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation of hematopoietic stem and progenitor cell (HSPC) pools. However, how Runx1 orchestrates self-renewal and lineage choices in combination with other factors is not well understood. Here we describe a genome-scale RNAi screen to detect genes that cooperate with Runx1 in regulating HSPCs. We identify the polycomb group protein Pcgf1 as an epigenetic regulator involved in hematopoietic cell differentiation. We show that simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while blocking differentiation of HSPCs in vitro. We find an upregulation of HoxA cluster genes upon Pcgf1 knockdown that possibly accounts for the increase in self-renewal. Further, our data suggest that cells lacking both Runx1 and Pcgf1 are blocked at an early progenitor stage, indicating that a concerted action of the transcription factor Runx1 together with the epigenetic repressor Pcgf1 is necessary for terminal differentiation. Thus, our work discovers a genetic link between transcriptional and epigenetic regulation that is required for hematopoietic differentiation. Hematopoietic stem and precursor cells freshly isolated from mice were transduced with an shRNA targeting Pcgf1 or a control shRNA. Cells were selected with puromycin for 36 h before total mRNA was isolated.
2012-06-17 | E-GEOD-33280 | biostudies-arrayexpress
Project description:The transcription factor Runx1 is essential for the establishment of definitive hematopoiesis during embryonic development. In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation of hematopoietic stem and progenitor cell (HSPC) pools. However, how Runx1 orchestrates self-renewal and lineage choices in combination with other factors is not well understood. Here we describe a genome-scale RNAi screen to detect genes that cooperate with Runx1 in regulating HSPCs. We identify the polycomb group protein Pcgf1 as an epigenetic regulator involved in hematopoietic cell differentiation. We show that simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while blocking differentiation of HSPCs in vitro. We find an upregulation of HoxA cluster genes upon Pcgf1 knockdown that possibly accounts for the increase in self-renewal. Further, our data suggest that cells lacking both Runx1 and Pcgf1 are blocked at an early progenitor stage, indicating that a concerted action of the transcription factor Runx1 together with the epigenetic repressor Pcgf1 is necessary for terminal differentiation. Thus, our work discovers a genetic link between transcriptional and epigenetic regulation that is required for hematopoietic differentiation.
2012-06-18 | GSE33280 | GEO
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
2019-11-12 | PXD007511 | Pride
Project description:Gene regulation by PCGF1 in hematopoietic progenitor cells
| PRJNA699535 | ENA
Project description:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes.
2009-05-20 | GSE16139 | GEO
Project description:Gene regulation by PCGF1 in hematopoietic progenitor cells [ChIP, MNaseSeq]
| PRJNA593952 | ENA
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Keywords: wildtype vs Myc-null
2007-06-30 | GSE7162 | GEO
Project description:Gene regulation by PCGF1 in hematopoietic progenitor cells [ChIP and MNaseSeq]
| PRJNA856871 | ENA
Project description:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes. Mouse hematopoietic stem cells were purified from bone marrow cells using negative and positive selection with a Magnetic-Activated Cell Sorter (MACS). total RNA and mRNA were purified from the purified cells using Trizol reagent and magnetic oligo dT beads. Double strand cDNAs were synthesized using a cDNA synthesis kit and anchored oligo dT primers. After NlaIII digestion, 3’ cDNAs were isolated and amplified through 16-cycle PCR. SAGE tags were released from the 3’ cDNA after linker ligation. Ditags were formed, concatemerized and cloned into a pZERO vector. Sequencing reactions were performed with the ET sequencing terminator kit. Sequences were collected using a Megabase 1000 sequencer. SAGE tag sequences were extracted using SAGE 2000 software.
2009-05-20 | E-GEOD-16139 | biostudies-arrayexpress