We provide a map of human ILC heterogeneity across multiple anatomical sites. Tissue-specific distinctions are particularly apparent for ILC1 populations, whose distribution was markedly altered in obesity or aging. Furthermore, the degree of ILC1 population hetero- geneity differed substantially in lymphoid versus mucosal sites. Together, these analyses comprise a comprehensive characterization of the spatial and temporal dynamics regulating the anatomical distri- bution, subset heterogeneity, and functional poten- tial of ILCs in non-diseased human tissues. Overall design: We present a quantitative analysis of ILC distribution and heterogeneity in lymphoid, mucosal, and metabolic tissues obtained from a diverse cohort of 44 previously non-diseased organ donors over a wide range of ages and body mass indexes (BMIs).
Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity.
Specimen part, Subject
View SamplesHTETOP cells, derived from the human fibrosarcoma cell line HT1080, express human topoisomearse II (TOP2A) exclusively from a tetracycline (TET)-regulated transgene, we used HTETOP cells to differentiate between TOP2A-dependent and independent apoptotic effects of doxorubicin and dexrazoxane.
Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.
Cell line
View SamplesWe wanted to determine how type II versus type III Toxoplasma infection affect host gene expression
Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
Cell line
View SamplesWe wanted to determine how type I ROP16 affect host gene expression
Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
Specimen part
View SamplesWe wanted to determine how type II Toxoplasma GRA15 and type I ROP16 affect host gene expression. We infected bone marrow-derived macrophages (BMMs) from B6 mice with type II (Pru), type II +ROP16 I, type II gra15, or type II gra15 + ROP16I.
Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
Specimen part, Treatment
View SamplesPregnane X receptor (PXR) is generally considered the most important sensor of natural and anthropogenic xenobiotics in vertebrates. In Xenopus, however, PXR plays a role in neural development and it is irresponsive to xenobiotics. We report a first broad-spectrum amphibian xenobiotic receptor, which is an ortholog of the mammalian constitutive androstane receptor (CAR). The low basal activity and pronounced responsiveness to activators such as drugs and steroids displayed by the Xenopus CAR resemble PXR, which both trace back to a common ancestor early in the divergence of land vertebrates. The constitutive activity of CAR emerged first in Sauropsida (reptiles and birds) and it is common to all fully terrestrial land vertebrates (Amniota). This activity can be mimicked by humanizing just two amino acids of the Xenopus CAR. These results demonstrate a remarkable plasticity of CAR which enabled its employment as Xenopus xenosensors. They open way to toxicogenomic and bioaugmentation studies in amphibians, a critically endangered taxon of land vertebrates. Taken together, we provide evidence for a much earlier origin of CAR, for its conservation in tetrapods which exceeds that of PXR, and for its remarkable functional plasticity which enabled its role as a PXR-like xenosensor in Amphibia.
Evolutionary history and functional characterization of the amphibian xenosensor CAR.
Sex, Specimen part, Treatment
View SamplesExtramedullary 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.
Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.
Sex, Specimen part
View SamplesThe aim of this study was to explore what molecular and cellular processes predicate the conversion from insulitis to diabetes. The transcriptional profiles of CD45+ immune cells collected from pancreas of a cohort of age-matched female mice, which were scanned by MRI to determine the risk of diabetes development.
Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging.
Sex, Age, Specimen part
View SamplesA data set of normal epithelium, serous ovarian surface epithelial-stromal tumors (benign and type II malignancies), stroma distal to tumor, and stroma adjacent to tumor (50 samples total). Additional cel files are included which represent replicate sampling from patients, and cel files that failed quality control but may be bioinformatically interesting. Additional replicate or failed cel files were not included in the final analysis (and so these samples were not included in the matrix).
Dysregulation of AKT3 along with a small panel of mRNAs stratifies high-grade serous ovarian cancer from both normal epithelia and benign tumor tissues.
Specimen part, Subject
View SamplesGene expression was compared between E18.5 E-cadherin conditional knockout (cKO) small intestine and E18.5 control mouse small intestine.
E-cadherin is required for intestinal morphogenesis in the mouse.
Specimen part
View Samples