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SRP111471
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
Reprogramming resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward towards the possibility of treating brain injuries or diseases. Here, we show that neurons reprogrammed using Ascl1, Lmx1a and Nurr1 functionally mature and integrate into existing brain circuitry, and that the majority of the reprogrammed neurons have properties of fast spiking, parvalbumin-containing interneurons. Overall design: A total of 6 samples were analyzed. Each sample is consists of approximately 33 laser-captured reprogrammed-neurons identified by nuclear GFP and expressing the transcription factors Ascl1, Lmx1a and Nurr1 (ALN).
Publication Title
Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 617 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced the mRNAs of embryonic stem cells (ESCs) cultured in different conditions. The two lines M (male) and F (female) used in this study were derived from E4 blastocysts of the same cross between a C57BL/6J (Mus musculus domesticus) and CAST/EiJ (Mus castaneus) male. mESCs were cultured in 2i and LIF as the ground state condition or in serum and LIF as the conventional condition. Epistem cell lines were also generated from the two lines by culturing them with Activin A and FGF2. In order to study more advanced development, we differentiated the two mESC lines through embryonic body formation to postmitotic motor neurons using retinoic acid and the smoothened agonist SAG. This differentiation process also results in the derivation of several types of interneurons. We picked single cells from all different conditions and generated sequencing libraries using the Smart-seq2 and Tn5 protocol. For simplicity, we designate the different condition as ES2i, ES, Epi and Neuron from hereon. We also obtained preimplantation inner cell mass and epiblast cells from E3.5 ICM (inner cell mass) and E4.5 blastocysts of the crossbred mice (male CAST/EiJ × female C57BL/6J) as well as postimplantation epiblast cells from E5.5 embryos of C57BL/6J mice Overall design: Examination of gene expression profile in individual male and female embryonic stem cell lines along developmental progression
Publication Title
Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 48 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene modules in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Module network analysis linked established regulators like Neurog3 to unrecognized roles in endocrine secretion and protein transport, and nominated multiple candidate regulators of pancreas development. Phenotyping mutant mice revealed that candidate regulatory genes encoding transcription factors, including Bcl11a, Etv1, Prdm16 and Runx1t1, are essential for pancreas development or glucose control. Our integrated approach provides a unique framework for identifying regulatory networks underlying pancreas development and diseases like diabetes mellitus.
Publication Title
An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.
Publication Title
Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone deacetylase inhibitors (HDACis) have been shown to potentiate hippocampal-dependent memory and synaptic plasticity and to ameliorate cognitive deficits and degeneration in animal models for different neuropsychiatric conditions. However, the impact of these drugs on hippocampal histone acetylation and gene expression profiles at the genomic level, and the molecular mechanisms that underlie their specificity and beneficial effects in neural tissue, remains obscure. Here, we mapped four relevant histone marks (H3K4me3, AcH3K9,14, AcH4K12 and pan-AcH2B) in hippocampal chromatin and investigated at the whole-genome level the impact of HDAC inhibition on acetylation profiles and basal and activity-driven gene expression. HDAC inhibition caused a dramatic histone hyperacetylation that was largely restricted to active loci pre-marked with H3K4me3 and AcH3K9,14. In addition, the comparison of Chromatin immunoprecipitation sequencing and gene expression profiles indicated that Trichostatin A-induced histone hyperacetylation, like histone hypoacetylation induced by histone acetyltransferase deficiency, had a modest impact on hippocampal gene expression and did not affect the transient transcriptional response to novelty exposure. However, HDAC inhibition caused the rapid induction of a homeostatic gene program related to chromatin deacetylation. These results illuminate both the relationship between hippocampal gene expression and histone acetylation and the mechanism of action of these important neuropsychiatric drugs.
Publication Title
Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina HiSeq 2000
Description
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))
Publication Title
De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. It is well known that CML cells are genetically unstable. However, the mechanisms by which these cells acquire genetic alterations are poorly understood. Imatinib mesylate (IM) is the standard therapy for newly diagnosed CML patients. IM targets the oncogenic kinase activity of BCR-ABL. Objective: To study the gene expression profile of BM hematopoietic cells in the same patients with CML before and one month after imatinib therapy. Methods: Samples from patients with CML were analyzed using Affymetrix GeneChip Expression Arrays. Results: A total of 594 differentially expressed genes, most of which (393 genes) were downregulated, as a result of imatinib therapy were observed. Conclusions: The blockade of oncoprotein Bcr-abl by imatinib could cause a decrease in the expression of key DNA repair genes, and cells try to restore the normal gene expression levels required for cell proliferation and chromosomal integrity.
Publication Title
Imatinib therapy of chronic myeloid leukemia restores the expression levels of key genes for DNA damage and cell-cycle progression.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Epidermal stem cells ensure that skin homeostasis is maintained. In murine skin, epidermal stem cells cluster at specific niches where, under steady-state conditions, they undergo cycles of dormancy and activation1. When cellular replenishment is required, epidermal stem cells egress from the niche and proliferate for a limited number of times to subsequently feed into the differentiated compartment1-3. However, only a subset of stem cells becomes active during each round of morphogenesis, suggesting that stem cells coexist in heterogeneous responsive states within the same niche. Using a circadian clock fluorescent reporter mouse model, we show that the dormant epidermal stem cell niche contains two coexisting populations of stem cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. In dormant niches, the core molecular clock protein Bmal1 transcriptionally modulates the expression of stem cell regulatory genes, including modulators of Wnt and TGFb, to create two coexisting stem cell populations, one predisposed, and the other less prone, to activation. Unbalancing this equilibrium of epidermal stem cells, through conditional epidermal deletion of Bmal1, resulted in a long-term progressive accumulation of non-responsive stem cells, premature impairment of tissue self-renewal, and a significant reduction in the development of squamous cell carcinomas. Our results indicate that the molecular clock machinery fine-tunes the spatiotemporal behavior of epidermal stem cells within their niche, and that perturbation of this mechanism affects tissue homeostasis and the predisposition to neoplastic transformation. The goals of this study was to compare the transcriptome of epidermal stem cells according to their circadian rhythm phase. We isolated epidermal stem cells (bulge cells; alpha6bright/CD34+ population) from 19 days old Per1-Venus mice and separated them according to Venusbright (clock positive) and Venus dim (clock negative). The goals of this study was to compare the transcriptome of epidermal stem cells in which their circadian rhythm machinery has been perturbed by deleting the gene that encodes for Bmal1. We compared the transcriptomes of basal interfollicular epidermis cells (alpha6 integrin bright/CD34- cells) from the dorsal skin of 1 year old BmalKO mice and their respective control littermates. Each array corresponds to purified cells from approximately 5 mice.
Publication Title
The circadian molecular clock creates epidermal stem cell heterogeneity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
The mammalian circadian clock system is made up of individual cell and tissue clocks that function as a coherent network, however it remains unclear which rhythmic functions of the liver clock are autonomous or rely on clocks in other tissues. Here, using mice which only have a functioning liver clock, we investigate the autonomous vs non-autonomous reatures of the liver clock and diurnal rhythmicity in the liver Overall design: 8-12 week-old, female WT, KO and Liver-RE BMAL1-stop-FL mice (see referenced paper for details) were fed ad libitum normal chow under 12hr light/ 12hr dark schedule. Livers were harvested every 4 hours over the circadian cycle at ZT0, 4, 8, 12, 16, 20 (n=3 per time point per group). Total RNA was extracted and used for RNA-seq.
Publication Title
Defining the Independence of the Liver Circadian Clock.
Sample Metadata Fields
Specimen part, Subject
View Samples