Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA271004 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We have shown that intravenous injection of HDAC3 floxed mice with adeno-associated virus (AAV) expressing Cre depletes hepatic HDAC3, upregulates lipogenic gene expression, and causes fatty liver. When AAV-Flag-HDAC3 wild-type (WT) is co-injected along with AAV-Cre, the exogenous HDAC3 is expressed at endogenous levels and can completely rescue fatty liver phenotype. Here we profile transcriptome of the rescued WT livers in comparison with HDAC3-depleted (KO) livers.
2013-11-25 | GSE49386 | GEO
Project description:We have shown that intravenous injection of HDAC3 floxed mice with adeno-associated virus (AAV) expressing Cre depletes hepatic HDAC3, upregulates lipogenic gene expression, and causes fatty liver. When AAV-Flag-HDAC3 wild-type (WT) is co-injected along with AAV-Cre, the exogenous HDAC3 is expressed at endogenous levels and can completely rescue fatty liver phenotype. Here we profile transcriptome of the rescued WT livers in comparison with HDAC3-depleted (KO) livers. 4-months old C57BL/6 male mice were co-injected with AAV-Cre or AAV-Cre plus AAV-Flag-HDAC3. Mice were fed ad libitum and harvested at 5 pm (ZT10) at 2-weeks post-injection. Liver total RNA was extracted and hybridized to Affymetrix Mouse Gene 1.0ST array.
2013-11-25 | E-GEOD-49386 | biostudies-arrayexpress
Project description:We utilized the Illumina MouseRef-8 gene expression technology to quantify differential gene expression between wildtype mice and mice with Osterix driven Cre conditional knockout of Hdac3 (Hdac3-CKO). We compared the RNA extracted from calvaria from 8 wildtype and 8 conditional knockout litter matched mice using two separate Illumina MouseRef-8 chips.
2010-03-27 | GSE21087 | GEO
Project description:We utilized the Illumina MouseRef-8 gene expression technology to quantify differential gene expression between wildtype mice and mice with Osterix driven Cre conditional knockout of Hdac3 (Hdac3-CKO). We compared the RNA extracted from calvaria from 8 wildtype and 8 conditional knockout litter matched mice using two separate Illumina MouseRef-8 chips. Mice with exon 7 of Hdac3 flanked by loxP sites were crossed with mice expressing Cre driven by the Osterix promoter. RNA from 5 day old mouse calvarial explants (digested for 20 minutes with collagenase) was purified using TRIzol according to the manufacturerâs protocol (Invitrogen) and reverse transcribed using Qiagenâs Quantitect Reverse Transcription Kit. Two independent microarray experiments were performed; each experiment used RNA from four wildtype and four conditional knockout litter matched mouse calvaria.
2010-04-07 | E-GEOD-21087 | biostudies-arrayexpress
Project description:Runx1 is highly expressed in osteoblasts, however, its function in osteogenesis is unclear. We generated mesenchymal progenitor-specific (Runx1f/fTwist2-Cre) and osteoblast-specific (Runx1f/fCol1α1-Cre) conditional knockout (Runx1 CKO) mice. The mutant CKO mice with normal skeletal development displayed a severe osteoporosis phenotype at postnatal and adult stages. Runx1 CKO resulted in decreased osteogenesis and increased adipogenesis. RNA-sequencing analysis, Western blot, and qPCR validation of Runx1 CKO samples showed that Runx1 regulates BMP signaling pathway and Wnt/β-catenin signaling pathway. ChIP assay revealed direct binding of Runx1 to the promoter regions of Bmp7, Alk3, and Atf4, and promoter mapping demonstrated that Runx1 upregulates their promoter activity through the binding regions. Bmp7 overexpression rescued Alk3, Runx2, and Atf4 expression in Runx1-deficient BMSCs. Runx2 expression was decreased while Runx1 was not changed in Alk3 deficient osteoblasts. Atf4 overexpression in Runx1-deficient BMSCs did not rescue expression of Runx1, Bmp7, and Alk3. Smad1/5/8 activity was vitally reduced in Runx1 CKO cells, indicating Runx1 positively regulates the Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 signaling pathway. Notably, Runx1 overexpression in Runx2-/- osteoblasts rescued expression of Atf4, OCN, and ALP to compensate Runx2 function. Runx1 CKO mice at various osteoblast differentiation stages reduced Wnt signaling and caused high expression of C/ebpα and Pparγ and largely increased adipogenesis. Co-culture of Runx1-deficient and wild-type cells demonstrated that Runx1 regulates osteoblast−adipocyte lineage commitment both cell-autonomously and non-autonomously. Notably, Runx1 overexpression rescued bone loss in OVX-induced osteoporosis. This study focused on the role of Runx1 in different cell populations with regards to BMP and Wnt signaling pathways and in the interacting network underlying bone homeostasis as well as adipogenesis, and has provided new insight and advancement of knowledge in skeletal development. Collectively, Runx1 maintains adult bone homeostasis from bone loss though up-regulating Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 and WNT/β-Catenin signaling pathways, and targeting Runx1 potentially leads to novel therapeutics for osteoporosis. Using unbiased genome-wide RNA-seq data from Runx1f/fCol1α1-Cre, Runx1ffTwist2-cre, Runx1f/f;Col2α1-Cre and their control osteoblasts, we examined Runx1-mediated transcriptional targets that could account for osteoblast differentiation defects and increased adipocytes.
2022-09-26 | GSE213930 | GEO
Project description:To assess the role of LSD1 in mouse small intestinal epithelium, we isolated small intestinal crypts and villus from wild type (WT) (Villin-Cre -; Lsd1f/f) and intestinal-epithelial-specific knock-out (cKO) (Villin-Cre+; Lsd1f/f) mice. This experiment uses a new Cre strain with 100% deletion efficiency. RNA was directly isolated from intestinal crypt and villus, and this was used for RNAseq. Gene expression analysis of cKO derived crypt and villus provides a spatially restricted outlook on the maturation status of the intestinal epithelium in the villi and the absence of Paneth cells in the crypt.
2023-08-02 | E-MTAB-10498 | biostudies-arrayexpress
Project description:Osteoblasts require substantial amounts of energy to synthesize bone matrix and coordinate the mineralization of the skeleton. This study analyzed the effect of mitochondrial dysfunction on bone formation in mouse limbs. The limb mesenchyme-specific Tfam knockout (Tfamf/f;Prx1-Cre: Tfam-cKO) mice were analyzed morphologically, and histologically and gene expression in the limb bones were assessed by in situ hybridization, quantitative real-time PCR and RNA sequencing. Moreover, we analyzed mitochondrial function of osteoblasts in Tfam-cKO mice by mitochondrial membrane potential assay and transmission electron microscopic (TEM) observations. We investigated the pathogenesis of spontaneous bone fractures by immunohistochemical analysis, TEM observations and biomechanical examination. The forelimbs in Tfam-cKO mice were significantly shortened from birth and occurred spontaneous fractures within the first week after birth, resulting in severe limb deformities. Histologically, bone hypoplasia with decrease of matrix mineralization was apparent, and the expressions of type Ⅰ collagen and osteocalcin were decreased in the osteoblasts of Tfam-cKO mice although Runx2 expression was unchanged. Decreased type Ⅰ collagen deposition and mineralization in the matrix of the limb bones in Tfam-cKO mice was associated with marked mitochondrial dysfunction. Biomechanical analysis showed significantly lower Young’s modulus and hardness due to poor apatite orientation in the bone tissue of Tfam-cKO mice. The mice with limb mesenchyme-specific Tfam deletion exhibited spontaneous limb bone fractures, resulting in severe limb deformities. Their bone fragility was caused by poor apatite orientation due to impaired osteoblasts differentiation and maturation.
2023-03-24 | GSE196628 | GEO
Project description:Comparison Between Sost-CreERT2 and wild type Cre- Gastrocnemius Skeletal Muscle Transcriptomes
| PRJNA490193 | ENA
Project description:We used Cd19-Cre to conditionally delete Hdac3 in order to define its role in germinal center B cells, which represent the cell of origin for many B cell malignancies. Cd19-Cre-Hdac3-/- mice showed impaired germinal center (GC) formation along with a defect in plasmablast generation. Analysis of Hdac3-/- GCs revealed a reduction in dark zone centroblasts and accumulation of light zone centrocytes. RNA-seq revealed a significant correlation between genes up-regulated upon Hdac3 loss and those up-regulated in Foxo1-deleted GC B cells, even though Foxo1 typically activates transcription. Therefore, to determine whether gene expression changes observed in Hdac3-/- GCs were a result of direct effects of Hdac3 deacetylase activity on transcription, we used an HDAC3 selective inhibitor to examine nascent transcription in germinal center-derived cell lines. Transcriptional changes upon HDAC3 inhibition in cells highly correlated with transcriptional changes observed in GCs in vivo. Further comparison of PRO-seq data with ChIP-seq/exo data for BCL6, SMRT, FOXO1 and H3K27ac identified direct targets of HDAC3 function including CD86, CD83 and CXCR5 that are likely responsible for driving the light zone phenotype observed in vivo.
2019-09-12 | GSE130502 | GEO
Project description:We used Cd19-Cre to conditionally delete Hdac3 in order to define its role in germinal center B cells, which represent the cell of origin for many B cell malignancies. Cd19-Cre-Hdac3-/- mice showed impaired germinal center (GC) formation along with a defect in plasmablast generation. Analysis of Hdac3-/- GCs revealed a reduction in dark zone centroblasts and accumulation of light zone centrocytes. RNA-seq revealed a significant correlation between genes up-regulated upon Hdac3 loss and those up-regulated in Foxo1-deleted GC B cells, even though Foxo1 typically activates transcription. Therefore, to determine whether gene expression changes observed in Hdac3-/- GCs were a result of direct effects of Hdac3 deacetylase activity on transcription, we used an HDAC3 selective inhibitor to examine nascent transcription in germinal center-derived cell lines. Transcriptional changes upon HDAC3 inhibition in cells highly correlated with transcriptional changes observed in GCs in vivo. Further comparison of PRO-seq data with ChIP-seq/exo data for BCL6, SMRT, FOXO1 and H3K27ac identified direct targets of HDAC3 function including CD86, CD83 and CXCR5 that are likely responsible for driving the light zone phenotype observed in vivo.
2019-09-12 | GSE130516 | GEO