The relative contribution of induced and natural Foxp3+ regulatory T cells (iTreg and nTreg cells, respectively) to the maintenance of tolerance is unknown. We examined their respective roles by in vivo adoptive transfer immunotherapy of newborn Foxp3-deficient BALB/c mice. Survival, weight gain, tissue infiltration, T cell activation, and the concentration of proinflammatory cytokines were used as outcome measurements. Treatment with iTreg cells alone was not successful. While effective in preventing death, treatment with nTreg cells alone was associated with chronic inflammation and autoimmunity. Outcomes markedly improved when conventional T (Tconv) cells were transferred together with the nTreg cells, where 10% of the peripheral Treg cell pool was derived by in-situ conversion. This enhancement depended upon the capacity of Tconv cells to express Foxp3.
A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity.
Age, Specimen part
View SamplesIdentification of all genes expressed by mouse olfactory sensory neurons; genes expressed in mature neurons, immature neurons, or both were distinguished. Independent validation of enrichment ratio values supported by statistical assessment of error rates was used to build a database of statistical probabilities of the expression of all mRNAs detected in mature neurons, immature neurons, both types of neurons (shared), and the residual population of all other cell types.
Genomics of mature and immature olfactory sensory neurons.
Sex, Specimen part
View SamplesIn development, timing is of the utmost importance, and the timing of various developmental processes are often changed during evolution.
Transcriptional neoteny in the human brain.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Specimen part
View SamplesSimilar temporal expression kinetics of transcription factors in human and mouse osteoclast differentiation evaluated by microarray
Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Specimen part
View SamplesHuman Immunodeficiency Virus (HIV) associated nephropathy (HIVAN) is characterized clinically by both nephrosis and by rapidly progressive kidney dysfunction. HIVAN is characterized histologically by both collapsing focal segmental glomerulosclerosis and prominent tubular damage. Neutrophil Gelatinase Associated Lipocalin (NGAL) is known to be rapidly expressed in distal segments of the nephron at the onset of different types of acute kidney injury, but few studies have examined NGAL in chronic kidney disease models. We found that urinary NGAL (uNGAL) was highly expressed by patients with biopsy proven HIVAN, whereas HIV+ patients without HIVAN demonstrated lower levels. uNGAL was also highly expressed in the TgFVB mouse model of HIVAN, which demonstrated NGAL gene expression in dilated, microcystic segments of the nephron. These data show that NGAL is markedly upregulated in the setting of HIVAN, and suggest that uNGAL levels may provide a non-invasive screening test to detect HIVAN related tubular disease.
Urinary NGAL marks cystic disease in HIV-associated nephropathy.
No sample metadata fields
View SamplesBarrier integrity is central to the maintenance of a healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic diseases such as food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD, we report that a fermentable fibre-rich diet alleviates AD severity and systemic allergen sensitization. The gut-skin axis underpins this phenomenon through SCFA, which strengthen skin barrier integrity by altering mitochondrial metabolism of epidermal keratinocytes. SCFA promote keratinocyte differentiation and the production of key structural lipids, resulting in enhanced barrier function. Our results demonstrate that dietary fibre and SCFA mitigate AD by improving barrier integrity, ultimately limiting early systemic allergen sensitization and development of disease. Overall design: 16 Samples, 4 groups in duplicate
Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation.
Genotype, Disease, Disease stage, Treatment, Subject
View SamplesThe main goal of our study is to identify the molecular events that determine the gonadal identity in mammals. Although testis and ovary arise from a common embryonic primordium, they represent outcomes of opposing fate determination. This decision to differentiate into a testis or an ovary hinges upon the balance between two antagonizing factors, pro-testis SOX9 and pro-ovary -catenin.
Gonadal Identity in the Absence of Pro-Testis Factor SOX9 and Pro-Ovary Factor Beta-Catenin in Mice.
Specimen part
View SamplesThrough deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor. Furthermore, miR-221 was required for tip cell proliferation and migration, as well as tip cell potential in mosaic blood vessels. miR-221 knockdown also prevented “hyper-angiogenesis” defects associated with Notch deficiency and miR-221 expression was inhibited by Notch signaling. Finally, miR-221 promoted tip cell behavior through repression of two targets: cyclin-dependent kinase inhibitor 1b (cdkn1b) and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1). These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis. Overall design: Identification of endothelial-expressed microRNA from FACS-isolated zebrafish endothelial cells.
miR-221 is required for endothelial tip cell behaviors during vascular development.
No sample metadata fields
View SamplesMicroRNAs (miRNAs) are short noncoding RNA molecules regulating the expression of mRNAs. Target identification of miRNAs is computationally difficult due to the relatively low homology between miRNAs and their targets. We present here an experimental approach to target identification where the cartilage-specific miR-140 was overexpressed and silenced in cells it is normally expressed in separate experiments. Expression of mRNAs was profiled in both experiments and the intersection of mRNAs repressed by miR-140 overexpression and derepressed by silencing of miR-140 was identified. The intersection contained only 49 genes, although both treatments affected the accumulation of hundreds of mRNAs. These 49 genes showed a very strong enrichment for the miR-140 seed sequence implying that the approach is efficient and specific. 21 of these 49 genes were predicted to be direct targets based on the presence of the seed sequence. Interestingly, none of these were predicted by the published target prediction methods we used. One of the potential target mRNAs, Cxcl12, was experimentally validated by Northern blot analysis and a luciferase reporter assay.
Experimental identification of microRNA-140 targets by silencing and overexpressing miR-140.
No sample metadata fields
View Samples