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GSE27605
Mus musculus
8 Downloadable Samples
Description
Using EphB2 or the ISC marker Lgr5, we have FACS-purified and profiled intestinal stem cells (ISCs), crypt proliferative progenitors and late transient amplifying cells to define a gene expression program specific for normal ISCs.
Publication Title
The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The perinatal period and early infancy are considered critical periods for lung development, and adversities during this period are believed to impact lung health in adulthood.The main factors affecting postnatal lung development and growth include environmental exposures, cigarette smoking, (viral) infections, allergic sensitization, and asthma.Therefore, we hypothesized that concomitant exposure in the early postnatal period in mice would cause more profound alterations in lung alveolarization and growth in adult life, quantified by stereology, and differently modulate lung inflammation and gene expression than either insult alone.Five-day-old male mice were immunized intraperitoneally (i.p.) with 10 µg of ovalbumin (OVA). This procedure was repeated at the 7th day of life, animals from the control group received i.p. injection of PBS only. Mice were exposed to either ambient PM2.5 or filtered air from the 5th to the 39th day of life, using an ambient particle concentrator developed at the Harvard School of Public Health (HAPC).Total RNA of lung samples (n=3 animals per group) was extracted using RNeasy Mini Kit (Qiagen, Hilden, Germany), according to manufacturer's instructions. The microarray analysis was performed using three RNA samples for each studied group (Control, OVA, PM2.5, OVA+PM2.5), totalizing 12 samples. One hundred nanograms of total RNA was amplified with the Ambion WT Expression Kit and hybridized onto the GeneChip Mouse Gene 2.0 ST Array (Thermo Scientific, Massachusetts, USA), following manufacturer’s protocol. The comparison between the control and OVA group exhibit 32 DEGs (28 up-regulated and 4 down-regulated), between the control and PM2.5 group had 6 DEGs (4 up and 2 down) and between the control and OVA+PM2.5 group had 5 DEGs (4 up and 1 down). The comparison between OVA and PM2.5 group showed 97 DEGS (22 up and 75 down) and between OVA and OVA+PM2.5 group had 7 DEGs (4 up and 3 down). Finally, the comparison between the PM2.5 and OVA+PM2.5 group exhibit 34 DEGs (2 up and 32 down).Our experimental data provide pathological support for the hypothesis that either allergic or environmental insults in early life have permanent adverse consequences to lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice.
Publication Title
Allergic sensitization and exposure to ambient air pollution beginning early in life lead to a COPD-like phenotype in young adult mice.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
The E-protein transcription factors E2A and HEB play important roles at several stages of hematopoiesis. However, the exact mechanism for theire action and the main targets in the LY6D negative common lymphoid progentior (CLP) compartment remains unknown. By adressing this question, we will gain important infromation regarding the early events leading to B-cell specification.
Publication Title
The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
In order to investigate molecular events involved in the regulation of lymphoid lineage commitment, we crossed lamda5 reporter transgenic mice to mice where the GFP gene is inserted into the Rag1 locus. This allowed us to sub-fractionate common lymphoid progenitors (CLPs) and pre-pro-B cells into lamda5-Rag1low, lamda5-Rag1high and lamda5+Rag1high cells. Clonal in vitro differentiation analysis demonstrated that Rag1low cells gave rise to B/T and NK cells. Rag1high cells displayed reduced NK-cell potential with preserved capacity to generate B- and T-lineage cells while the lamda5+ cells were B-lineage restricted. Ebf1 and Pax5 expression was largely confined to the Rag1high populations. These cells also expressed a higher level of the surface protein LY6D providing an additional tool for the analysis of early lymphoid development. These data suggest that the classical CLP compartment composes a mixture of cells with more or less restricted lineage potentials opening new possibilities to investigate early hematopoiesis.
Publication Title
Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
BALB/c mice are susceptible to proteoglycan (PG) aggrecan-induced arthritis (PGIA), a murine model of rheumatoid arthritis (Glant,T.T. and Mikecz,K., Proteoglycan aggrecan-induced arthritis. A murine autoimmune model of rheumatoid arthritis. Methods Mol.Med. 2004. 102: 313-338.). However, there are marked differences among BALB/c colonies (maintained by different vendors at different locations) in PGIA onset and severity, which could be the result of subtle variations in their genetic background.
Publication Title
BALB/c mice genetically susceptible to proteoglycan-induced arthritis and spondylitis show colony-dependent differences in disease penetrance.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Breast cancer metastasis to bone is a critical determinant of long-term survival after treatment of primary tumors. We used a mouse model of spontaneous bone metastasis to determine new molecular mechanisms. Differential transcriptome comparisons of primary and metastatic tumor cells revealed that a substantial set of genes suppressed in bone metastases were highly enriched for promoter elements for the type I interferon (IFN) regulatory factor, Irf7, itself suppressed in mouse and human metastases. The critical function of the Irf7 pathway was demonstrated by restoration of exogenous Irf7 or systemic interferon administration, which significantly reduced bone metastases and prolonged metastasis-free survival. Using mice deficient in the type I receptor (Ifnar1-/-) or mature B, T and NK cell responses (NOD Scid IL-2r-/- mice), we demonstrated that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. Metastasis suppression correlated with decreased accumulation of myeloid-derived suppressor cells and increased CD4++, CD8 T cells and NK cells in the peripheral blood and was reversed by depletion of CD8+ cells and NK cells. Clinical importance of our findings was demonstrated as increased primary tumor Irf7 expression predicted prolonged bone and lung metastasis-free survival. Thus we report for the first time, a novel innate immune pathway, intrinsic to breast cancer cells, whose suppression in turn restricts systemic immunosurveillance to enable metastasis. This pathway may constitute a novel therapeutic target for restricting breast cancer metastases.
Publication Title
Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
In order to identify the targets of GATA4-FOG2 action in mammalian heart development we performed Affymetrix microarray comparisons of gene expression in normal and mutant at embryonic (E) day E12.5 hearts. We compared RNA samples from both Fog2-null and Gata4ki/ki mutant E12.5 hearts to the wild-type control E12.5 hearts. We reasoned that as the phenotypes of the Fog2 knockout and Gata4ki/ki mutation (a V217G mutation that specifically cripples the interaction between GATA4 and FOG proteins) are similar, we should expect to identify a similar set of differentially expressed genes in both experiments. As an additional control, we expected to find the Fog2 gene expression absent in the mutant (null) Fog2 cardiac sample, but not Gata4ki/ki sample.
Publication Title
Cardiac expression of Tnnt1 requires the GATA4-FOG2 transcription complex.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 42 Downloadable Samples
Description
Transcriptome analysis of mRNA samples from a cohort of mice with histopathologically diagnosed Undifferentiated Myeloid Leukemia.
Publication Title
Analyzing tumor heterogeneity and driver genes in single myeloid leukemia cells with SBCapSeq.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
Publication Title
The epidermal differentiation-associated Grainyhead gene Get1/Grhl3 also regulates urothelial differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
Publication Title
The epidermal differentiation-associated Grainyhead gene Get1/Grhl3 also regulates urothelial differentiation.
Sample Metadata Fields
Specimen part
View Samples