Hopx is a transcription co-factor expressed during lung development and we wanted to profile Hopx +/+ and -/- embyonic lungs. Results inform the role of Hopx in embryonic lung development
Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.
Specimen part, Cell line, Treatment
View SamplesProgenitor cells require coordinated expression of lineage-specific programs, and the nuclear lamina has emerged as an important scaffold for organizing chromatin in many cell types. These transcriptome profiling experiments accompany a study focused on defining nuclear organization changes during cardiac development. This dataset defines gene expression changes induced by Hdac3 deletion during early stages of cardiogenesis, modeled using ESC differentiation assays.
Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.
Cell line, Treatment
View SamplesMutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of familial and sporadic Parkinsons disease (PD). Here, we investigated in parallel gene and microRNA transcriptome profiles of three different LRRK2 mouse models. Striatal tissue was isolated from adult LRRK2 knockout mice, as well as mice expressinghuman LRRK2 wildtype (hLRRK2-WT) or PD-associated R1441G mutation (hLRRK2-R1441G).
Gene and MicroRNA transcriptome analysis of Parkinson's related LRRK2 mouse models.
Age, Specimen part
View SamplesWe use mice containing a gene trap in the first intron of the Rest gene, which effectively eliminates transcription from all coding exons, to prematurely remove REST from neural progenitors. We find catastrophic DNA damage that occurs during S-phase of the cell cycle and concominant with activation of p53 pro-apoptotic sgnalling, with consequences including abnormal chromosome separation, apoptosis, and smaller brains.
The REST remodeling complex protects genomic integrity during embryonic neurogenesis.
Specimen part
View SamplesWe use mice containing a gene trap in the first intron of the Rest gene, which effectively eliminates transcription from all coding exons, to prematurely remove REST from neural progenitors. We find catastrophic DNA damage that occurs during S-phase of the cell cycle, with consequences including abnormal chromosome separation, apoptosis, and smaller brains. Further support for persistent effects is the latent appearance of proneural glioblastomas in adult mice also lacking the tumor suppressor, p53. A Rest deficient mouse line generated previously, using a conventional gene targeting approach, does not exhibit these phenotypes, likely due to a remaining C terminal peptide that still binds chromatin and recruits REST chromatin modifiers.Our results indicate that REST-mediated chromatin remodeling is required for proper S-phase dynamics, prior to its well-established role in relieving repression of neuronal genes at terminal differentiation.
The REST remodeling complex protects genomic integrity during embryonic neurogenesis.
Specimen part
View SamplesMicroglia are key regulators of inflammatory response after stroke and brain injury. Here we profiled the microglia transcriptome isolated from a spontaneously hypertensive rat model of focal cerebral ischemia.
Transcriptomic characterization of microglia activation in a rat model of ischemic stroke.
Sex, Age
View SamplesOcular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)- and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFN, FasL and CD8+ T cells but not perforin or TNF were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFN and FasL did not target tumor cells directly as the majority of SPLNX IFNR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNR1. Bone marrow chimeras showed that immune cell expression of IFNR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFN- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFN- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors.
Splenectomy promotes indirect elimination of intraocular tumors by CD8+ T cells that is associated with IFNγ- and Fas/FasL-dependent activation of intratumoral macrophages.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene-expression signature of vascular invasion in hepatocellular carcinoma.
Sex, Age, Specimen part
View SamplesNGS was used in order to discover novel downstream targets of the miR-17-92/106b clusters. Overall design: Comperasion of gene expression from miR-17-92/106b KO and control
miR-17-92 and miR-106b-25 clusters regulate beta cell mitotic checkpoint and insulin secretion in mice.
Specimen part, Cell line, Subject
View Samples