To understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury.
Analysis of factorial time-course microarrays with application to a clinical study of burn injury.
Sex, Disease
View SamplesThe study goals are to utilize error-correcting molecular barcodes to accurately quantify transcriptomes. Conventional RNA-Seq studies with small input amounts suffer from amplification artifacts that impact downstream analyses. Random nucleotide barcodes have been used as a marker for unique molecules, but errors during PCR and sequencing negatively impact the quantification accuracy. We use error-correcting molecular barcodes to mitigate these errors and apply them to bulk mRNA and single cell transcriptomes.
No associated publication
Sex, Age, Specimen part, Disease, Cell line
View SamplesLong recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an alternatively activated phenotype. TAM differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.
The cellular and molecular origin of tumor-associated macrophages.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel Foxo1-dependent transcriptional programs control T(reg) cell function.
Specimen part
View SamplesWildtype B6, Rag1-/- B6 and Rag1-/- B6 mice harboring the 225.4 IgA producing hybridoma were colonized for 10 days with Bacteroides thetaiotaomicron
IgA response to symbiotic bacteria as a mediator of gut homeostasis.
No sample metadata fields
View SamplesMemory T cells provide immunity against pathogen reinvasion, but mechanisms of their long-term maintenance is unclear. Here we show that mice with the deletion of the transcription factor Foxo1 in activated CD8+ T cells had defective secondary but not primary responses to Listeria monocytogenes infection. Compared to short-lived effector T cells, memory precursor effector T cells expressed higher amounts of Foxo1 that promoted their generation and maintenance. Gene expression profiling and chromatin immunoprecipitation sequencing experiments revealed the chemokine receptor CCR7 and the transcription factor TCF1 as novel Foxo1-bound target genes with critical functions in memory T cell trafficking and transcriptional regulation. These findings demonstrate that Foxo1 is selectively incorporated into the genetic program that regulates memory but not effector CD8+ T cell responses to infection.
The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection.
Specimen part
View SamplesRegulatory T (Treg) cells characterized by expression of the transcription factor forkhead box P3 (Foxp3) maintain immune homeostasis by suppressing self-destructive immune responses1-4. Foxp3 operates as a late acting differentiation factor controlling Treg cell homeostasis and function5, whereas the early Treg cell lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors6-10. However, whether Foxo proteins act beyond the Treg cell commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1, and display reduced T-cell receptor-induced Akt activation, Foxo1 phosphorylation, and Foxo1 nuclear exclusion. Mice with Treg cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the proinflammatory cytokine Ifng, that do not appear to be directly regulated by Foxp3. These findings demonstrate that the evolutionarily ancient Akt-Foxo1 signaling module controls a novel genetic program indispensable for Treg cell function.
Novel Foxo1-dependent transcriptional programs control T(reg) cell function.
Specimen part
View SamplesMouse lung cancers were generated using the KrasLA model, in which a latent mutated Kras2 allele (resulting in the amino acid substitution G12D) is sporadically activated through spontaneous homologous recombination. These mice develop lung adenomas with full penetrance; over time, the tumors acquire morphologic characteristics reminiscent of those of human adenocarcinoma, such as nuclear atypia and a high mitotic index.
An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis.
Specimen part
View SamplesLandmark events occur in a coordinated manner during preimplantation development of the mammalian embryo, yet the regulatory network that orchestrates these events remains largely unknown.
An Oct4-Sall4-Nanog network controls developmental progression in the pre-implantation mouse embryo.
No sample metadata fields
View Samples