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accession-icon GSE86181
Evidence of two distinct functionally specialized fibroblast lineages in breast stroma
  • organism-icon Homo sapiens
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

Background: The terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma. Methods: The two lineages are prospectively isolated by FACS based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271low/MUC1high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase stained cultures. Results: Lobular fibroblasts are CD105high/CD26low while interlobular fibroblasts are CD105low/CD26high. Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors. Conclusions: Two distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that lobular fibroblasts constitute a specialized microenvironment for human breast luminal epithelial progenitors, i.e. the putative precursors of breast cancer.

Publication Title

Evidence of two distinct functionally specialized fibroblast lineages in breast stroma.

Sample Metadata Fields

Specimen part

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accession-icon GSE95613
Expression data from Drosophila tumor models
  • organism-icon Drosophila melanogaster
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Drosophila Gene 1.0 ST Array (drogene10st)

Description

Epithelial tumors can progress from a benign tissue overgrowth (hyperplasia) to a malignant neoplastic tumor, which is characterized by an increase in motility and invasiveness. The Cohen laboratory has developed an epithelial tumor model in which overexpression of the epidermal growth factor receptor gene (EGFR) leads to benign tissue hyperplasia. When combined with other cooperating factors, EGFR overexpression can lead to neoplasia and malignant metastasis.

Publication Title

Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer.

Sample Metadata Fields

Specimen part, Time

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accession-icon GSE37485
Expression data of pre-stasis cultured HMEC
  • organism-icon Homo sapiens
  • sample-icon 52 Downloadable Samples
  • Technology Badge Icon Affymetrix HT Human Genome U133A Array (hthgu133a)

Description

We have generated a large collection of normal human mammary epithelial cell strains from women aged 16 to 91 years, derived from primary tissues, to enable functional and molecular interrogation of aging. We demonstrate in finite-lifespan cultured and uncultured epithelial cells that aging is associated with reduction of myoepithelial cells and with increases in luminal cells expressing keratin 14 and integrin 6, traits that are expressed exclusively in myoepithelial cells in women under 30. We find that changes to the luminal lineage result from age-dependent expansion of multipotent progenitors that bear defects resulting in incompletely differentiated luminal cells. These findings were verified in vivo in normal breast tissues. Myoepithelial cells have been suggested to act as tumor suppressors, and progenitor cells are implicated as the etiological roots of mammary carcinomas. Thus with aging there is a shift in the balance of luminal/myoepithelial lineages, and changes in the functional spectrum of multipotent progenitors, which presages increased potential for malignant transformation.

Publication Title

Accumulation of multipotent progenitors with a basal differentiation bias during aging of human mammary epithelia.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE46246
[E-MEXP-3786] IGF-I-induced chronic gliosis and retinal stress lead to neurodegeneration in an animal model of retinopathy
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

Transcription profiling by array of mouse male retinas to investigate IGF-I-induced chronic gliosis and retinal stress

Publication Title

Insulin-like growth factor I (IGF-I)-induced chronic gliosis and retinal stress lead to neurodegeneration in a mouse model of retinopathy.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP136058
Gene expression in PANC1 cells treated with Rakicidin
  • organism-icon Homo sapiens
  • sample-icon 36 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

Cells were treated with Rakicidin A or an analogue compound BE-43547 or DMSO (control) in three replicates. Overall design: three groups in triplicates.

Publication Title

APD-Containing Cyclolipodepsipeptides Target Mitochondrial Function in Hypoxic Cancer Cells.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon GSE39152
Molecular signature of brain resident memory CD8+ T cells
  • organism-icon Mus musculus
  • sample-icon 13 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Tissue resident memory (Trm) represent a newly described memory T cell population. We have previously characterized a population of Trm that persists within the brain following acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm do not undergo recall expansion following dissociation from the tissue. Furthermore, these Trm do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells we compared the gene-expression profiles of Trm isolated from the brain to circulating memory T cells isolated from the spleen following an acute virus infection. Trm displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors and overexpressed several inhibitory receptors. Cumulatively, these data indicates that Trm are a distinct memory T cell population disconnected from the circulating memory T cell pool and displaying a unique molecular signature which likely results in optimal survival and function within their local environment.

Publication Title

The molecular signature of tissue resident memory CD8 T cells isolated from the brain.

Sample Metadata Fields

Specimen part

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accession-icon GSE61732
Human Staufen1 associates to miRNAs involved in neuronal cell differentiation and is required for correct dendritic formation
  • organism-icon Homo sapiens
  • sample-icon 7 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Double-stranded RNA-binding proteins are key elements in the intracellular localization of mRNA and its local translation. Staufen is a double-stranded RNA binding protein involved in the localised translation of specific mRNAs during Drosophila early development and neuronal cell fate. The human homologue Staufen1 forms RNA-containing complexes that include proteins involved in translation and motor proteins to allow their movement within the cell, but the mechanism underlying translation repression in these complexes is poorly understood. Here we show that human Staufen1-containing complexes contain essential elements of the gene silencing apparatus, like Ago1-3 proteins, and we describe a set of miRNAs specifically associated to complexes containing human Staufen1. Among these, miR124 stands out as particularly relevant because it appears enriched in human Staufen1 complexes and is over-expressed upon differentiation of human neuroblastoma cells in vitro. In agreement with these findings, we show that expression of human Staufen1 is essential for proper dendritic arborisation during neuroblastoma cell differentiation, yet it is not necessary for maintenance of the differentiated state, and suggest potential human Staufen1 mRNA targets involved in this process.

Publication Title

Human Staufen1 associates to miRNAs involved in neuronal cell differentiation and is required for correct dendritic formation.

Sample Metadata Fields

Cell line

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accession-icon GSE4709
Gcn4p-mediated transcriptional stress response
  • organism-icon Saccharomyces cerevisiae
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Yeast Genome 2.0 Array (yeast2)

Description

The transcriptional data from an integrative analysis of transcriptional and metabolic stress responses that provides a more complete understanding of the mechanisms by which genetic regulatory circuits mediate metabolic phenotype.

Publication Title

Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP171142
Gene expression profile in Liver of old mice after 5 weeks of Heterocronic parabiosis with Yg WT or Yg MANFHet mice
  • organism-icon Mus musculus
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 4000

Description

To ask whether MANF contributes to the rejuvenating effects of heterochronic parabiosis, we generated heterochronic pairs in which 20 month old WT mice were combined with either 4 month old MANFHet (O-YgHet) or WT (O-YgWT) littermates, and maintained for 5 weeks before analysis. Control pairs in which old WT mice were combined together (O-O) were used. Livers were collected from each animal in the pair and RNA was sequenced for 5 independent animals/condition. Overall design: RNA was extracted and sequenced for 5 animals/condition

Publication Title

MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage.

Sample Metadata Fields

Age, Subject

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accession-icon GSE18326
Role of FoxO3 in adult neural stem cell maintenance in mice
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

In the nervous system, neural stem cells (NSC) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3-/- mice have fewer NSC in vivo than wild type counterparts. NSC isolated from adult FoxO3-/- mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSC suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSC might have important implications for counteracting brain aging in long-lived species.

Publication Title

FoxO3 regulates neural stem cell homeostasis.

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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