Murine NK cells were compared at rest and following 24 hours of IL-15 stimulation for their mRNA expression profiles on the Affymetrix MOE430_2 microarray platform. Additional comparators included resting bulk splenocytes.
Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs.
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View SamplesNK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. Utilizing an NK cell-specific miR-15/16 deficient genetic model (15aKO), we identified a critical role for miR-15/16 family microRNAs in the normal maturation of NK cells in vivo, with a specific reduction in mature CD11b+CD27- NK cells in multiple tissues. The mechanism responsible was a block in differentiation, since accelerated NK cell death was not evident, and earlier intermediates of NK cell maturation were expanded. Further, we identified Myb as a direct target of miR-15/16 in NK cells, with Myb expression increased in immature 15aKO NK cells. Following adoptive transfer, immature 15aKO NK cells exhibited defective maturation, which was rescued by ectopic miR-15/16 expression or Myb knockdown. Moreover, Myb overexpression resulted in defective NK cell maturation. Thus, miR-15/16 regulation of Myb controls the normal NK cell maturation program.
MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.
Cell line
View SamplesNK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. Utilizing an NK cell-specific miR-15/16 deficient genetic model (15aKO), we identified a critical role for miR-15/16 family microRNAs in the normal maturation of NK cells in vivo, with a specific reduction in mature CD11b+CD27- NK cells in multiple tissues. The mechanism responsible was a block in differentiation, since accelerated NK cell death was not evident, and earlier intermediates of NK cell maturation were expanded. Further, we identified Myb as a direct target of miR-15/16 in NK cells, with Myb expression increased in immature 15aKO NK cells. Following adoptive transfer, immature 15aKO NK cells exhibited defective maturation, which was rescued by ectopic miR-15/16 expression or Myb knockdown. Moreover, Myb overexpression resulted in defective NK cell maturation. Thus, miR-15/16 regulation of Myb controls the normal NK cell maturation program.
MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional code and disease map for adult retinal cell types.
Specimen part
View SamplesBrain circuits are assembled from a large variety of morphologically and functionally diverse cell types. It is not known how the intermingled cell types of individual brain regions differ in their expressed genomes. Here we describe an atlas of cell type transcriptomes of the adult retina. We found that each adult cell type expresses a specific set of genes, including a unique set of transcription factors, forming a barcode for cell identity. Cell type transcriptomes carry enough information to categorize cells into corresponding morphological classes and types. Surprisingly, several barcode genes are eye disease-associated genes that we demonstrate to be specifically expressed not only in photoreceptors but also in particular retinal circuit elements such as inhibitory neurons as well as in retinal microglia. Our data suggest that distinct cell types of individual brain regions are characterized by marked differences in their expressed genomes.
Transcriptional code and disease map for adult retinal cell types.
Specimen part
View SamplesBrain circuits are assembled from a large variety of morphologically and functionally diverse cell types. It is not known how the intermingled cell types of individual brain regions differ in their expressed genomes. Here we describe an atlas of cell type transcriptomes of the adult retina. We found that each adult cell type expresses a specific set of genes, including a unique set of transcription factors, forming a barcode for cell identity. Cell type transcriptomes carry enough information to categorize cells into corresponding morphological classes and types. Surprisingly, several barcode genes are eye disease-associated genes that we demonstrate to be specifically expressed not only in photoreceptors but also in particular retinal circuit elements such as inhibitory neurons as well as in retinal microglia. Our data suggest that distinct cell types of individual brain regions are characterized by marked differences in their expressed genomes.
Transcriptional code and disease map for adult retinal cell types.
Specimen part
View SamplesWe performed a single-cell transcriptome analysis of double-negative developing thymocytes from the DN2, DN3 and DN4 populations Overall design: Double-negative developing thymocytes from the DN2, DN3 and DN4 populations were sorted from six WT mice and used for single cell RNA Seq (10x genomics platform)
The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection.
Sex, Specimen part, Cell line, Subject
View SamplesWe performed a transcriptome comparison of double-negative developing thymocytes from the DN3-4 population, from mice overexpressing the transcription factor Duxbl and wild type mice Overall design: Double-negative developing thymocytes from both WT and Duxbl[ind]xpTa[Cre] mice were gated for CD4-, CD8-, CD3-, B220-, CD25int, CD44low and CD117low expression, which define the DN3-4 stage of thymocyte development. The experiment was performed in four replicates, giving a total of 8 samples.
The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection.
Sex, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell competition is a tumour suppressor mechanism in the thymus.
Specimen part
View SamplesLeukemia cells are considered developmentally 'frozen', and their phenotype is thought to reflect their stage of origin. To gain insights into the cell population from which T-ALL arises, we compared by global gene expression profiling T-ALL samples (n = 10) to different stages of T cell development, following the order from early thymic progenitor (ETP), to triple negative (TN) TN2, to TN3, to TN4, to immature single positive (ISP), to double positive (DP) thymocytes.
Cell competition is a tumour suppressor mechanism in the thymus.
Specimen part
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