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GSE57220
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hematopoietic stem cells (HSCs) are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR) is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential is variably supported by different Steel factor (SF)-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings suggest a new molecular basis for HSC control and expansion.
Publication Title
Distinct stromal cell factor combinations can separately control hematopoietic stem cell survival, proliferation, and self-renewal.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse haematopoietic stem cells (HSCs) undergo a post-natal transition in several properties, including a marked reduction in their self-renewal activity. We now show that the developmentally timed change in this key function of HSCs is associated with their decreased expression of Lin28b and an accompanying increase in their let-7 microRNA levels. Lentivirus(LV)-mediated overexpression of Lin28 in adult HSCs elevates their self-renewal activity in transplanted irradiated hosts, as does overexpression of Hmga2, a well-established let-7 target that is upregulated in fetal HSCs. Conversely, HSCs from fetal Hmga2-/- mice do not display the heightened self-renewal activity that is characteristic of wild-type fetal HSCs. Interestingly, overexpression of Hmga2 in adult HSCs does not mimic the ability of elevated Lin28 to activate a fetal lymphoid differentiation program. Thus Lin28b may act as a master regulator of developmentally timed changes in HSC programs with Hmga2 serving as its specific downstream modulator of HSC self-renewal potential.
Publication Title
The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSC) sustain long-term reconstitution of hematopoiesis in primary transplantation recipients. Few HSC can serially reconstitute secondary recipients, and their identity and contribution to normal hematopoiesis remain moot. We directed transgene expression to a distinct fraction of HSC in the adult bone marrow. Epxression of the reporter transgene segregated with reconstituting activity during secondary transplantations. The labeled cells had an undifferentiated phenotype and expression profile, were slow-cycling and localized to the vascular niche. Inducible genetic labeling showed the transgene-expressing HSC gave rise to other cells within the HSC populations, confirming their top position in the differentiation hierarchy. Importantly, labeled HSC gave rise to more than two-thirds of all myeloid cells and platelets in adult mice, and this contribution could be further accelerated by interferon response. Thus, the rare "top-level" HSC with serial reconstitution capacity also serve as the major source of endogenous hematopoiesis in adult animals. Overall design: Sorted LSK CD48- CD150+ Map17-GFP+ and Map17-GFP- HSCs and LSK CD48+ CD150- Map17-GFP-MPPs were sequenced for mRNA profiling.
Publication Title
Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Two types of adipose tissues, white and brown, are found in mammals. Increasingly novel strategies are being proposed for the treatment of obesity and its associated complications by altering amount and/or activity of BAT using mouse models.
Publication Title
Microarray based gene expression analysis of murine brown and subcutaneous adipose tissue: significance with human.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disorder caused by dystrophin deficiency. Previous work suggested that increased expression of the dystrophin-related protein utrophin in the mdx mouse model of DMD can prevent dystrophic pathophysiology. Physiological tests showed that the transgenic mouse muscle functioned in a way similar to normal muscle. More recently, it has become possible to analyse disease pathways using microarrays, a sensitive method to evaluate the efficacy of a therapeutic approach. We thus examined the gene expression profile of mdx mouse muscle compared to normal mouse muscle and compared the data with that obtained from the transgenic line expressing utrophin. The data confirm that the expression of utrophin in the mdx mouse muscle results in a gene expression profile virtually identical to that seen for the normal mouse. This study confirms that a strategy to up-regulate utrophin is likely to be effective in preventing the disease.
Publication Title
Microarray analysis of mdx mice expressing high levels of utrophin: therapeutic implications for dystrophin deficiency.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this, the question of whether such forms of bystander T cell activation occur during immune responses is hotly debated.
Publication Title
Human CD4+ memory T cells are preferential targets for bystander activation and apoptosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines, however uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild type replication activity at sites not expressing the relevant microRNA.
Publication Title
MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
Oligodendrocyte precursor cells from postnatal day 10 optic nerve remained in a developmentally immature state in LIF-/- mice. Partial recovery of myelin genes is seen in LIF-/- mice by postnatal day 14 in the optic nerve. Very little difference in myelin genes in the optic nerve is seen by postnatal day 35 (adult).
Publication Title
Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 46 Downloadable Samples
- Illumina HiSeq 2000
Description
The mammalian suprachiasmatic nucleus (SCN) drives daily rhythmic behavior and physiology, yet a detailed understanding of its coordinated transcriptional programmes is lacking. To reveal the true nature of circadian variation in the mammalian SCN transcriptome we combined laser-capture microdissection (LCM) and RNA-Seq over a 24-hour light / dark cycle. We show that 7-times more genes exhibited a classic sinusoidal expression signature than previously observed in the SCN. Another group of 766 genes unexpectedly peaked twice, near both the start and end of the dark phase; this twin-peaking group is significantly enriched for synaptic transmission genes that are crucial for light-induced phase-shifting of the circadian clock. 342 intergenic non-coding RNAs, together with novel exons of annotated protein-coding genes, including Cry1, also show specific circadian expression variation. Overall, our data provide an important chronobiological resource (www.wgpembroke.com/shiny/SCNseq/) and allow us to propose that transcriptional timing in the SCN is gating clock resetting mechanisms. Overall design: Pooled dissected tissue of the suprachiasmatic nucleus from five adult male mice provided one of three replicates for each of six timepoints over a 12:12 light/dark (LD) cycle (ZT2, 6, 10, 14, 18 and 22). Each biological replicate was sequenced over 3 seperate lanes using Illumina HiSeq.
Publication Title
Temporal transcriptomics suggest that twin-peaking genes reset the clock.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
In the normal mouse the pituitary gonadotrophins determine development, maturation and physiological regulation of the testis with follicle-stimulating hormone (FSH) activating the Sertoli cell and luteinising hormone (LH) the Leydig cell. To look at the potential interaction of cell types within the testis following hormone stimulation we have investigated the effect of rFSH on testicular gene expression in the hypogonadal (hpg) male mouse. Due to a deletion in the gene encoding gonadotrophin-releasing hormone (GnRH), FSH and LH levels are at the lower limit of detection in the circulation and mice remain in a pre-pubertal state throughout life unless given exogenous hormone.
Publication Title
Effects of FSH on testicular mRNA transcript levels in the hypogonadal mouse.
Sample Metadata Fields
No sample metadata fields
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