Thrombospondin 1 (TSP-1) is an anti-angiogenic matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and gene microarray analyses on a mouse model of induced colitis.
Thrombospondin-1 type 1 repeats in a model of inflammatory bowel disease: transcript profile and therapeutic effects.
Specimen part
View SamplesING1b and GADD45a are nuclear proteins involved in the regulation of cell growth, apoptosis and DNA repair. We previously found that ING1b is required to target GADD45a-mediated active DNA-demethylation via TET1 to specific loci. In order to study the impact of ING1-GADD45a on gene expression, we compared the expression profile of wildtype mouse embryonic fibroblasts (MEFs) with Ing1- and Gadd45a- single- or double-knockout (DKO) MEFs. Overall design: Gene expression profiling in all 4 genotypes of undifferentiated MEFs in triplicates.
Impaired DNA demethylation of C/EBP sites causes premature aging.
Sex, Specimen part, Cell line, Subject
View SamplesCD25+ regulatory T cells develop in the thymus (nTregs), but may also be generated in the periphery upon stimulation of naive CD4 T cells under appropriate conditions (iTregs). The mechanisms that regulate the generation of peripheral iTregs are largely unknown.
Analysis of the transcriptional program of developing induced regulatory T cells.
Specimen part, Treatment, Subject, Time
View SamplesTBI was induced with lateral fluid-percussion injury in adult male rats. Genome-wide RNA-seq of the perilesional cortex, ipsilateral thalamus and dorsal hippocampus was performed at 3 months post-TBI. The data highlighted chronic transcriptional changes, particularly, in the perilesional cortex and thalamus. Genes showing a significantly altered expression both in the cortex and thalamus were submitted to the LINCS web query to identify novel pharmacotherapies to improve post-TBI outcome. Overall design: TBI was induced to 5 rats, 5 sham operated served as a controls.
Analysis of Post-Traumatic Brain Injury Gene Expression Signature Reveals Tubulins, Nfe2l2, Nfkb, Cd44, and S100a4 as Treatment Targets.
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View SamplesSelf-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engrafted in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them.
Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells.
Specimen part
View SamplesGlucocorticoids (GC) are used as first line therapies for generalized suppression of inflammation (e.g. allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work has revealed that GC induced a stable anti-inflammatory phenotype in monocytes, the glucocorticoid-stimulated monocytes (GCsM) that we now exploited for targeted GC-mediated therapeutic effects.
Immune suppression via glucocorticoid-stimulated monocytes: a novel mechanism to cope with inflammation.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesSox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in human, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/-catenin dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog (HH) signaling completely prevents BCC formation and leads to a progressive loss of oncogene expressing cells. Transcriptional profiling of oncogene expressing cells with Sox9 deletion, combined with in vivo ChIP-sequencing uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix (ECM) deposition and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that links tumor initiation and invasion.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesThree human ER+ breast cancer cell lines--MCF-7, T47-D, BT-474--grown with or without estradiol (E2).
GREB 1 is a critical regulator of hormone dependent breast cancer growth.
Cell line
View SamplesWe describe the preparation, evaluation, and application of an S100A12 protein-conjugated solid support, hereafter the “A12-resin,” that can remove 99% of Zn(II) from complex biological solutions without significantly perturbing the concentrations of other metal ions. The A12-resin can be applied to selectively deplete Zn(II) from diverse tissue culture media and from other biological fluids including human sera. To further demonstrate the utility of this approach, we investigated metabolic, transcriptomic, and metallomic responses of HEK293T cells cultured in medium depleted of Zn(II) using S100A12. Our data indicate that dividing cells can maintain a constant pool of free Zn(II), even under conditions of severe Zn(II) deprivation. We expect that the A12-resin will facilitate interrogation of disrupted Zn(II) homeostasis in biological settings, uncovering novel roles for Zn(II) in biology. Overall design: Defining the response of a cell line to Zn(II) starvation
A Method for Selective Depletion of Zn(II) Ions from Complex Biological Media and Evaluation of Cellular Consequences of Zn(II) Deficiency.
Cell line, Subject
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