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accession-icon SRP064758
Nuclear retention of mRNA in mammalian tissues
  • organism-icon Mus musculus
  • sample-icon 119 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Messenger RNA is thought to predominantly reside in the cytoplasm, where it is translated and eventually degraded. Although nuclear retention of mRNA has a regulatory potential it is considered extremely rare in mammals. Here to explore the extent of mRNA retention in metabolic tissues we combine deep sequencing of nuclear and cytoplasmic RNA fractions with single molecule transcript imaging in mouse beta cells, liver and gut. We identify a wide range of protein coding genes for which the levels of spliced polyadenylated mRNA are higher in the nucleus than in the cytoplasm. These include genes such as the transcription factor ChREBP, Nlrp6, Glucokinase and Glucagon receptor. We demonstrate that nuclear retention of mRNA can efficiently buffer cytoplasmic transcript levels from noise that emanates from transcriptional bursts. Our study challenges the view that transcripts predominantly reside in the cytoplasm and reveals a role of the nucleus in dampening gene expression noise. Overall design: we have total of 8 samples all are mice. liver nuclear RNA (2 replicates), liver cytoplasmic RNA (2 replicates), MIN6 (cell line) nuclear RNA (2 replicates), MIN6 (cell line) cytoplasmic RNA (2 replicates)

Publication Title

Nuclear Retention of mRNA in Mammalian Tissues.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon SRP078795
Single-cell spatial reconstruction reveals global division of labor in the mammalian liver
  • organism-icon Mus musculus
  • sample-icon 26 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

The mammalian liver consists of hexagonal-shaped lobules, radially polarized by blood flow and morphogens. Key liver genes have been shown to be differentially expressed along the lobule axis, a phenomenon termed zonation, but a detailed genome-wide reconstruction of this spatial division of labor has not been achieved. Here we measure the whole transcriptome of thousands of single mouse liver cells and infer their lobule coordinates using a panel of zonated landmark genes, characterized with single-molecule FISH. We obtain a genome-wide reconstruction of liver zonation profiles with unprecedented spatial resolution. We find that more than 50% of liver genes are significantly zonated and uncover abundant non-monotonic profiles that peak at the mid-lobule layers. Our approach can facilitate reconstruction of similar spatial genomic blueprints for other mammalian organs. Overall design: mRNA profiles from single cells extracted from mouse liver were generated by deep sequencing of 1736 of single cells, sequenced in several batches in an Illumina NextSeq.

Publication Title

Single-cell spatial reconstruction reveals global division of labour in the mammalian liver.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE54206
Growth factor independence 1b (Gfi1b) is required for erythroid cell maturation and regulates embryonic globin expression
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression.

Sample Metadata Fields

Specimen part

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accession-icon GSE54204
Growth factor independence 1b (Gfi1b) is required for erythroid cell maturation and regulates embryonic globin expression [MoGene-1_0]
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Growth factor independence 1b (Gfi1b) is a DNA binding repressor of transcription with vital functions in hematopoiesis. Gfi1b-null embryos die at midgestation very likely due to defects in erythro- and megakaryopoiesis. To analyze the full functionality of Gfi1b in embryonic erythropoiesis, we used conditionally deficient mice that harbor floxed Gfi1b alleles and one EpoR-Cre knock-in allele.

Publication Title

Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression.

Sample Metadata Fields

Specimen part

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accession-icon GSE54205
Growth factor independence 1b (Gfi1b) is required for erythroid cell maturation and regulates embryonic globin expression [Mouse430_2]
  • organism-icon Mus musculus
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Growth factor independence 1b (Gfi1b) is a DNA binding repressor of transcription with vital functions in hematopoiesis. Gfi1b-null embryos die at midgestation very likely due to defects in erythro- and megakaryopoiesis. To analyze the full functionality of Gfi1b in erythropoiesis, we used conditionally deficient mice that harbor floxed Gfi1b alleles and the Mx-Cre transgene inducible by pIpC treatment.

Publication Title

Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression.

Sample Metadata Fields

Specimen part

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accession-icon GSE36427
KLF1, KLF2 and c-myc control a regulatory network essential for embryonic erythropoiesis
  • organism-icon Mus musculus
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

The Krppel-like factors, KLF1 and KLF2, positively regulate embryonic -globin expression, and have additional overlapping roles in embryonic (primitive) erythropoiesis. KLF1-/-KLF2-/- double knockout mice are anemic at embryonic day 10.5 (E10.5) and die by E11.5, in contrast to single knockouts. To investigate the combined roles of KLF1 and KLF2 in primitive erythropoiesis, expression profiling of E9.5 erythroid cells was performed. A limited number of genes had a significantly decreasing trend of expression in wild-type, KLF1-/- and KLF1-/-KLF2-/-. Among these, c-myc emerged as a central node in the most significant gene network. c-myc expression is synergistically regulated by KLF1 and KLF2, and both factors bind the c-myc promoters. To characterize the role of c-myc in primitive erythropoiesis, ablation was performed specifically in mouse embryonic proerythroblast cells. After E9.5, these embryos exhibit an arrest in the normal expansion of circulating red cells and develop anemia analogous to KLF1-/-KLF2-/-. In the absence of c-myc, circulating erythroid cells do not show the normal increase in - and -like globin expression, but interestingly, have accelerated erythroid maturation, between E9.5 and E11.5. This study reveals a novel regulatory network by which KLF1 and KLF2 regulate c-myc, to control the primitive erythropoietic program.

Publication Title

Kruppel-like factor 1 (KLF1), KLF2, and Myc control a regulatory network essential for embryonic erythropoiesis.

Sample Metadata Fields

Specimen part

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accession-icon GSE15062
Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizers upon combined TNFR1/LTBR NF-kB signaling
  • organism-icon Mus musculus
  • sample-icon 21 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Mouse aorta smooth muscle cells (SMCs) express TNF receptor superfamily member 1A (TNFR1) and lymphotoxin receptor (LTR). Circumstantial evidence has linked the SMC LTR to tertiary lymphoid organogenesis in diseased aortae of hyperlipidemic mice. Here, we explored potential roles of TNFR1 and LTR activation in cultured SMCs. TNFR1 signaling by TNF activated the classical RelA NF-B pathway, whereas LTR signaling by agonistic anti LTR antibody activated both the classical RelA and alternative RelB NF-B pathways. Addition of both agonists synergized to enhance p100 inhibitor processing to the p52 subunit of NF-B and promoted its nuclear translocation suggesting RelA-RelB cross-talk in transcription regulation. Correspondingly, microarrays showed that simultaneous TNFR1 and LTR activation when compared to activation of single receptors was followed by markedly elevated levels of mRNAs encoding leukocyte homeostatic chemokines CCL2, CCL5, CXCL1, and CX3CL1. Furthermore, SMCs acquired prototypical features of mesenchymal cells known as lymphoid tissue organizers (LTOs), which control tertiary lymphoid organogenesis in autoimmune diseases, through hyperinduction of CCL7, CCL9, CXCL13, CCL19, CXCL16, VCAM-1, and ICAM-1. Experiments with ltbr-/- SMCs suggested that the LTR-RelB activation component of NF-B signaling was obligatory to generate the LTO phenotype. TNFR1-LTR crosstalk also resulted in augmented synthesis and prolonged secretion of lymphorganogenic chemokine proteins into the culture medium. Thus, combined TNFR1-LTR signaling triggers SMC transdifferentiation into a phenotype that strikingly resembles LTOs. LTO-like SMCs may adopt a thus far unrecognized role in diseased arteries, i.e. to coordinate tertiary lymphoid organogenesis in atherosclerosis, aortic aneurysm, and transplant vasculopathy.

Publication Title

Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizer-like cells on combined tumor necrosis factor receptor-1/lymphotoxin beta-receptor NF-kappaB signaling.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE19139
Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizers upon combined TNFR1/LTBR NF-kB signaling
  • organism-icon Mus musculus
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Cultured mouse aorta endothelial cells (from 8-12 weeks old C57BL/6J mice, passage 2-3) were exposed to phosphate buffered saline (control) or a combination of TNFalpha plus agonistic alpha-LTR antibody for 24 hours as described in Ltzer et al. 2009. Arterioscler. Thromb. Vasc. Biol., in press. Total RNA was extracted and microarrays were prepared.

Publication Title

Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizer-like cells on combined tumor necrosis factor receptor-1/lymphotoxin beta-receptor NF-kappaB signaling.

Sample Metadata Fields

Specimen part

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accession-icon GSE24207
mRNA analysis in different mouse tissues
  • organism-icon Mus musculus
  • sample-icon 73 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

The functioning of a specific tissue depends on the expression pattern of the different genes. We used microarrays to compare gene expression across different murine tissues, to get a better understanding in the expression pattern and functioning of the different tissues. With this analysis, we were not only able to identify genes that were specifically expressed in a spicific tissue but, as important, we also identified genes that were specifically repressed in a tissue, compared to al the other analysed tissues.

Publication Title

Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE24940
Transcription in adult mouse tissues
  • organism-icon Mus musculus
  • sample-icon 40 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

We used Affymetrix Gene Arrays (1.0 ST) to compare gene expression across different murine tissues.

Publication Title

Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation.

Sample Metadata Fields

Specimen part

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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