Activators of innate immunity may have potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin (IL)-22, which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection, and thus holds promise as a broad-spectrum antiviral agent. Overall design: Total mRNA from intestinal epithelial cells of Rag1-/- mice treated with PBS, IL-18, IL-22 or IL-22/IL-18 was assayed for RNA sequencing.
Viral infection. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18.
No sample metadata fields
View SamplesThe goal of this project is to identify genes preferentially expressed in inflammatory macrophages as compared with control macrophages.
Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.
Specimen part, Time
View SamplesSOX2 is the main gene involved in anophthalmia. In order to identify genes regulated by SOX2 transcription factors (genes that could be good candidates to also be involved in ocular development), we studied transcriptomic profiles of murine genetically modified stem cells overexpressing the RAX gene (CCE-Rx cells) after transfection by a siRNA against SOX2 or a scramble siRNA.
Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.
Specimen part, Time
View SamplesWe developed a method to convert gene expression signatures across the Illumina and Affymetrix platforms.
Cross-platform prediction of gene expression signatures.
Specimen part
View SamplesRetinoic acid (RA) is a potent inducer of cell differentiation and plays an essential role in sex-specific germ cell development in the mammalian gonad. RA is essential for male gametogenesis and hence fertility. However, RA can also disrupt sexual cell fate in somatic cells of the testis, promoting transdifferentiation of male Sertoli cells to female granulosa-like cells when the male sexual regulator Dmrt1 is absent. The feminizing ability of RA in the somatic testis suggests that RA might normally play a role in somatic cell differentiation or cell fate maintenance in the ovary. To test for this possibility we disrupted RA signaling in somatic cells of the early fetal ovary using three genetic strategies and one pharmaceutical approach. We found that deleting all three RA receptors (RARs) in the XX somatic gonad at the time of sex determination did not significantly affect ovarian differentiation, follicle development, or female fertility. Transcriptome analysis of adult triple mutant ovaries revealed remarkably little effect on gene expression in the absence of somatic RAR function. Likewise, deletion of three RA synthesis enzymes (Aldha1-3) at the time of sex determination did not masculinize the ovary. A dominant-negative RAR transgene altered granulosa cell proliferation, likely due to interference with a non-RA signaling pathway, but did not affect granulosa cell specification or fertility. Finally, culture of fetal XX gonads with an RAR antagonist blocked germ cell meiotic initiation but did not disrupt sex-biased gene expression. We conclude that RA signaling, although crucial in the ovary for meiotic initiation, is not required for granulosa cell specification, differentiation, or reproductive function. Overall design: Ovaries from six week old mice with five replicates in each of two genotypes were analyzed by RNA-Seq
Retinoic acid signaling is dispensable for somatic development and function in the mammalian ovary.
Age, Specimen part, Cell line, Subject
View SamplesSignatures of Oncogenic Pathway Deregulation in Human Cancers.
Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
No sample metadata fields
View SamplesSignatures of Oncogenic Pathway Deregulation in Human Cancers.
Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
No sample metadata fields
View SamplesSignatures of Oncogenic Pathway Deregulation in Human Cancers.
Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
No sample metadata fields
View SamplesSignatures of Oncogenic Pathway Deregulation in Human Cancers
Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
No sample metadata fields
View Samples