We sequenced mRNA from three age groups (3months (3M), 24 months (24M) and 29 months (29M)) from the full hippocampus Overall design: There were two independent experiments: 3M vs 24M (n=5 to 6, single-end sequencing) and 3M vs 29M (n=3, paired-end sequencing))
De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus.
No sample metadata fields
View SamplesThis study analyzed mRNA profiles in rhombomere 4 of E10.5 mouse knock-in embryos expressing either normal endogenous Hox-B1 protein or the paralogous Hox-A1 protein from the Hoxb1 locus. The Hox-A1 protein was found to be detectably less efficacious than Hox-B1 in promoting neurogenesis in the basal plate of rhombomere 4 and its transcriptional profile shared several similarities with the Hoxb1 mutant.
Reversal of Hox1 gene subfunctionalization in the mouse.
No sample metadata fields
View SamplesHoxb1 is required for proper specification of rhombomere 4 and the facial motor neurons. This study analyzed gene expression in the corresponding hindbrain segment of E10.5 mutant embryos. Several genetic pathways were found altered, including transcription factors such as Phox2b, Gata3, Nkx2-2 and Nkx6-1.
Reversal of Hox1 gene subfunctionalization in the mouse.
No sample metadata fields
View SamplesWe tested how complete or partial loss of endophilin A1, A2 and A3 affects gene expression in mouse hippocampus. Total loss of endophilin (triple knock-outs, TKO) was assessed in newborn mice, since the TKO mice only survive only several hours after birth. Partial loss of endophilin (endoA1,A2 double knock-out, DKO) was assessed between Overall design: 2-3 weeks of age (p13-21).
Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes Dysregulation of Autophagy and the Ubiquitin-Proteasome System.
Subject
View SamplesSynovial sarcoma-like tumors were generated in mice by conditionally expressing the human t(X;18) translocation-derived SYT-SSX2 fusion protein. Using a Tamoxifen-inducible CreER system, we show here that sporadic expression of SYT-SSX2 across multiple tissue types leads to exclusive formation of synovial sarcoma-like tumors while its widespread expression is lethal. CreER-based sporadic expression both avoids the severe early developmental phenotypes associated with widespread SYT-SSX2 expression and better models natural pathogenesis of cancers where transformed cells usually arise within an environment of largely normal cells.
A CreER-based random induction strategy for modeling translocation-associated sarcomas in mice.
No sample metadata fields
View SamplesThe human SYT-SSX fusion protein was expressed in a developmentally dependent fashion in murine myoblasts. Tumors harvested from mice in adolescence were compared to normal mouse skeletal muscle samples.
A conditional mouse model of synovial sarcoma: insights into a myogenic origin.
No sample metadata fields
View SamplesProfile gene expression from tumors that develop in mice bearing conditional activation of EWS-ATF1, compared to control mouse tissues from the chest wall as well as tumor samples from mouse models of synovial sarcoma and osteosarcoma achieved by conditional disruption of Rb1 and p53 Overall design: 13 clear cell sarcomas (5 started with Rosa26CreER, 4 with TATCre, 2 with Prx1CreERT2, and 2 with Bmi1IRESCreERT2), 7 osteosarcomas, 6 synovial sarcomas, 6 control samples
Modeling clear cell sarcomagenesis in the mouse: cell of origin differentiation state impacts tumor characteristics.
Specimen part, Subject
View SamplesAging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer''s Disease (AD). An effective therapy does not yet exist. Here we use mouse models for age-associated memory impairment and amyloid deposition to study transcriptome and cell type-specific epigenome plasticity at the systems level in the brain and in peripheral organs. We show that at the level of epigenetic gene-expression aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region. While inflammation is associated with increased gene-expression that is linked to a subset of transcription factors, de-regulation of plasticity genes is mediated via different mechanisms in the amyloid and the aging model. Amyloid pathology impairs histone-acetylation and decreases expression of plasticity genes while aging affects differential splicing that is linked to altered H4K12 acetylation at the intron-exon junction in neurons but not in non-neuronal cells. We furthermore show that oral administration of the clinically approved histone deacetylase inhibitor Vorinostat not only restores spatial memory, but also exhibits an anti-inflammatory action and reinstates epigenetic balance and transcriptional homeostasis at the level of gene expression and exon usage. This is the first systems-level investigation of transcriptome plasticity in the hippocampal CA1 region in aging and AD models and of the effects of an orally dosed histone deacetylase inhibitor. Our data has important implications for the development of minimally invasive and cost-effective therapeutic strategies against age-associated cognitive decline. In fact, our data strongly suggest to test Vorinostat in patients suffering from AD. Overall design: mRNA profile from aged (CA1 and liver) and APP/PS1 (CA1) animals treated with oral vehicle or SAHA for 4 weeks
HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models.
No sample metadata fields
View SamplesWe sequenced mRNA from 24 samples extracted from mouse CA1 tissue to generate the first CA1-specific murine transcriptome and the first CA1-transcriptome in response to environmental novelty under normal and Kat2a-loss-of-function conditions. Overall design: Samples were divded in 4 groups: A: Control naïve (n=6), B: control novelty-exposed (n=5), C: Kat2a cKO naïve (n=6), D: Kat2a cKO novelty-exposed (n=7). Pairwise comparisons for AvsB, AvsC, BvsD and CvsD were performed using DESeq2.
K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation.
No sample metadata fields
View SamplesWe sequenced small RNAs from 12 samples extracted from mouse CA1 tissue to generate the first CA1-specific murine miRNome under normal and Kat2a-loss-of-function conditions. Overall design: Samples were divded in 4 groups: A: Control (n=6), C: Kat2a cKO naïve (n=6)
K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation.
No sample metadata fields
View Samples