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accession-icon SRP153334
The homeobox transcription factor HB9 induces senescence and blocks differentiation in hematopoietic stem and progenitor cells
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

The translocation t(7;12)(q36;p13) occurs in infants and very young children with AML and usually has a fatal prognosis. Whereas the transcription factor ETV6, located at chromosome 12p13, has largely been studied in different leukemia types, the influence of the translocation partner HB9 (chr. 7q36), is still unknown. This is particularly surprising as ectopic expression of HB9 is the only recurrent molecular hallmark of translocation t(7;12) AML. We investigated the influence of HB9 as a potential oncogene on cell proliferation and cell cycle in vitro, as well as on hematopoietic stem cell differentiation in vivo using murine and human model systems. We show, that HB9 induces premature senescence in human HT1080 and murine NIH3T3 cells, providing for the first time evidence for an oncogenic potential of HB9. Furthermore, HB9-transduced primary murine hematopoietic stem and progenitor cells underwent a profound differentiation arrest and accumulated at the megakaryocyte/erythrocyte progenitor stage, resulting in a premalignant myeloid cell population in vivo. Concomitantly, HB9 expression upregulates erythropoiesis-related genes in primary human hematopoietic stem and progenitor cells, and enriches gene expression profiles for cell cycle and mitosis-related biological processes. In summary, the novel findings of HB9 dependent premature senescence and perturbed hematopoietic differentiation shed light on the oncogenic properties of HB9 in translocation t(7;12) AML and offer novel targets for therapeutic intervention. Overall design: CD34+ cells were transduced with either GFP or HB9

Publication Title

The homeobox transcription factor HB9 induces senescence and blocks differentiation in hematopoietic stem and progenitor cells.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE24795
Gene Expression differences between replication error deficient and proficient colorectal cancers: the dominant role of deletions in 3UTR poly T sequences
  • organism-icon Homo sapiens
  • sample-icon 27 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

16 replication error proficient (RER-/MSI-) and 14 replication error deficient (RER+/MSI+) colorectal cancer cell lines

Publication Title

Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT sequence deletions.

Sample Metadata Fields

Cell line

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accession-icon GSE36947
Elevating Sox2 levels deleteriously affects the growth of glioblastoma and medulloblastoma cells.
  • organism-icon Homo sapiens
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Induction of the transcription factor Sox2 from a doxycycline-inducible promoter in iSox2-DAOY medulloblastoma cells.

Publication Title

Elevating SOX2 levels deleteriously affects the growth of medulloblastoma and glioblastoma cells.

Sample Metadata Fields

Specimen part

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accession-icon GSE15680
Laser microdissection of Arabidopsis cells at the powdery mildew infection site
  • organism-icon Arabidopsis thaliana
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

To elucidate host processes and components required for the sustained growth and reproduction of the obligate biotrophic fungus Golovinomyces orontii on Arabidopsis thaliana, laser microdissection was used to isolate cells at the site of infection at 5 days postinfection for downstream global Arabidopsis expression profiling. Site-specific profiling increased sensitivity dramatically, allowing us to identify specific host processes, process components, and their putative regulators hidden in previous whole-leaf global expression analyses. For example, 67 transcription factors exhibited altered expression at the powdery mildew (PM) infection site, with subsets of these playing known or inferred roles in photosynthesis, cold/dehydration responses, defense, auxin signaling, and the cell cycle. Using integrated informatics analyses, we constructed putative regulatory networks for a subset of these processes and provided strong support for host cell cycle modulation at the PM infection site. Further experimentation revealed induced host endoreduplication occurred exclusively at the infection site and led us to identify MYB3R4 as a transcriptional regulator of this process. Induced endoreduplication was abrogated in myb3r4 mutants, and G. orontii growth and reproduction were reduced. This suggests that, by increasing gene copy number, localized endoreduplication serves as a mechanism to meet the enhanced metabolic demands imposed by the fungus, which acquires all its nutrients from the plant host.

Publication Title

Laser microdissection of Arabidopsis cells at the powdery mildew infection site reveals site-specific processes and regulators.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE77474
Intestinal myofibroblast vs skin fibroblast
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumour progression. Myofibroblasts have previously mostly been distinguished from normal fibroblasts only by the expression of smooth muscle actin (SMA). We now identify AOC3, a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast reacting monoclonal antibody (mAb), PR2D3. The normal and tumour tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used for FACS sorting of myofibroblasts obtained by non-enzymatic procedures. Whole genome microarray mRNA expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly expressed differentially between these two cell types; NKX2-3 and LRRC17 are expressed in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts. Transforming Growth Factor (TGF) substantially down-regulated AOC3 expression in myofibroblasts but not in skin fibroblasts, in which it dramatically increased the expression of SMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of myofibroblast-related gene expression and an increased expression of the fibroblast associated gene, SHOX2, suggesting that NKX2-3 is a key mediator for maintaining myofibroblast characteristics. Our results show that colorectal myofibroblasts, as defined by the expression of AOC3, NKX2-3 and other markers, are a distinctly different cell type from TGF activated fibroblasts.

Publication Title

Myofibroblasts are distinguished from activated skin fibroblasts by the expression of AOC3 and other associated markers.

Sample Metadata Fields

Specimen part

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accession-icon GSE40973
Expression profiling of uninfected and Golovinomyces orontii infected Arabidopsis thaliana wild type Col-0 and del1-1 mutant
  • organism-icon Arabidopsis thaliana
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

In plants, the activation of immunity is often inversely correlated with growth. Mechanisms that plant growth in the context of pathogen challenge and immunity are unclear. Investigating Arabidopsis infection with the powdery mildew fungus, we find that the Arabidopsis atypical E2F DEL1, a transcriptional repressor known to promote cell proliferation, represses accumulation of the hormone salicylic acid (SA), an established regulator of plant immunity. DEL1 deficient plants are more resistant to pathogens and slightly smaller than wild type. The resistance and size phenotypes of DEL1 deficient plants are due to the induction of SA and activation of immunity in the absence of pathogen challenge. Moreover, Enhanced Disease Susceptibility 5 (EDS5), a SA transporter required for elevated SA and immunity, is a direct repressed target of DEL1. Together, these findings indicate that DEL1 control of SA levels contributes to regulating the balance between growth and immunity in developing leaves.

Publication Title

Atypical E2F transcriptional repressor DEL1 acts at the intersection of plant growth and immunity by controlling the hormone salicylic acid.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE4926
Gene expression profiling of a mouse model of islet dysmorphogenesis
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

In the past decade, several transcription factors critical for pancreas development have been identified. Despite this success, many of the cell surface and extracellular factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor HNF6 specifically in the pancreatic endocrine cell lineage resulted in the disruption of islet morphogenesis, including dysfunctional endocrine cell sorting, increased islet size, and failure of islets to migrate away from the ductal epithelium. We exploited the dysmorphic islets in pdx1PBHnf6 animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal pancreas tissue from wild type and pdx1PBHnf6 animals. We report the identification of genes with an altered expression in HNF6 Tg animals and highlight factors with potential importance in islet morphogenesis.

Publication Title

Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis.

Sample Metadata Fields

Specimen part

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accession-icon E-MEXP-1195
Transcription profiling of rat to investigate effects of hyperglycaemi and genetic background on gene expression
  • organism-icon Rattus norvegicus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Expression 230A Array (rae230a)

Description

Effects of hyperglycaemia and genetic background differences on renal gene expression

Publication Title

Comparative analysis of methods for gene transcription profiling data derived from different microarray technologies in rat and mouse models of diabetes.

Sample Metadata Fields

Sex, Age, Specimen part, Disease, Subject

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accession-icon GSE90607
Fibrostenotic phenotype of fibroblasts in Crohn's disease is dependent on tissue stiffness and reversed by LOX inhibition
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

The results of this study indicate that stenotic fibroblasts exhibit an aberrant response to tissue stiffness with reduced MMP activity, leading to a perpetuous vicious circle of ever more fibrosis formation. Altering the microenvironment by LOX inhibition increases MMP activity and decreases ECM contraction, resulting in a potential anti-fibrotic agent for Crohns disease.

Publication Title

Fibrostenotic Phenotype of Myofibroblasts in Crohn's Disease is Dependent on Tissue Stiffness and Reversed by LOX Inhibition.

Sample Metadata Fields

Sex, Specimen part, Disease, Subject

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accession-icon GSE6966
Transcriptional profiling of bipotential embryonic liver cells to identify liver progenitor cell surface markers.
  • organism-icon Mus musculus
  • sample-icon 19 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Transcriptional profiling of bipotential embryonic liver cells to identify liver progenitor cell surface markers.

Sample Metadata Fields

Specimen part, Cell line

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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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