| 1. |
- Bagger, Frederik Otzen, et al.
(författare)
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HemaExplorer: a database of mRNA expression profiles in normal and malignant haematopoiesis.
- 2013
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 41:D1, s. 1034-1039
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Tidskriftsartikel (refereegranskat)abstract
- The HemaExplorer (http://servers.binf.ku.dk/hemaexplorer) is a curated database of processed mRNA Gene expression profiles (GEPs) that provides an easy display of gene expression in haematopoietic cells. HemaExplorer contains GEPs derived from mouse/human haematopoietic stem and progenitor cells as well as from more differentiated cell types. Moreover, data from distinct subtypes of human acute myeloid leukemia is included in the database allowing researchers to directly compare gene expression of leukemic cells with those of their closest normal counterpart. Normalization and batch correction lead to full integrity of the data in the database. The HemaExplorer has comprehensive visualization interface that can make it useful as a daily tool for biologists and cancer researchers to assess the expression patterns of genes encountered in research or literature. HemaExplorer is relevant for all research within the fields of leukemia, immunology, cell differentiation and the biology of the haematopoietic system.
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| 2. |
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| 3. |
- Knudsen, Kasper Jermiin, et al.
(författare)
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ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.
- 2015
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Ingår i: Genes & Development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 29:18, s. 1915-1929
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Tidskriftsartikel (refereegranskat)abstract
- The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors that serve to restrict HSC differentiation. In the present work, we identify ETS (E-twenty-six)-related gene (ERG) as a critical factor protecting HSCs from differentiation. Specifically, loss of Erg accelerates HSC differentiation by >20-fold, thus leading to rapid depletion of immunophenotypic and functional HSCs. Molecularly, we could demonstrate that ERG, in addition to promoting the expression of HSC self-renewal genes, also represses a group of MYC targets, thereby explaining why Erg loss closely mimics Myc overexpression. Consistently, the BET domain inhibitor CPI-203, known to repress Myc expression, confers a partial phenotypic rescue. In summary, ERG plays a critical role in coordinating the balance between self-renewal and differentiation of HSCs.
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| 4. |
- Rapin, Nicolas, et al.
(författare)
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Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 123:6, s. 894-904
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Tidskriftsartikel (refereegranskat)abstract
- Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal hematopoietic hierarchy, using expression profiles from normal stem/progenitor cells, and next mapped the AML patient samples to this landscape. This allowed us to identify the closest normal counterpart of individual AML samples and determine gene expression changes between cancer and normal. We find the cancer vs normal method (CvN method) to be superior to conventional methods in stratifying AML patients with aberrant karyotype and in identifying common aberrant transcriptional programs with potential importance for AML etiology. Moreover, the CvN method uncovered a novel poor-outcome subtype of normal-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.
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| 5. |
- Schwenzer, Susanne P., et al.
(författare)
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Fluids during diagenesis and sulfate vein formation in sediments at Gale crater, Mars
- 2016
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Ingår i: Meteoritics and Planetary Science. - : Wiley. - 1086-9379 .- 1945-5100. ; 51:11, s. 2175-2202
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Tidskriftsartikel (refereegranskat)abstract
- We model the fluids involved in the alteration processes recorded in the Sheepbed Member mudstones of Yellowknife Bay (YKB), Gale crater, Mars, as revealed by the Mars Science Laboratory Curiosity rover investigations. We compare the Gale crater waters with fluids modeled for shergottites, nakhlites, and the ancient meteorite ALH 84001, as well as rocks analyzed by the Mars Exploration rovers, and with terrestrial ground and surface waters. The aqueous solution present during sediment alteration associated with phyllosilicate formation at Gale was high in Na, K, and Si; had low Mg, Fe, and Al concentrations—relative to terrestrial groundwaters such as the Deccan Traps and other modeled Mars fluids; and had near neutral to alkaline pH. Ca and S species were present in the 10−3 to 10−2 concentration range. A fluid local to Gale crater strata produced the alteration products observed by Curiosity and subsequent evaporation of this groundwater-type fluid formed impure sulfate- and silica-rich deposits—veins or horizons. In a second, separate stage of alteration, partial dissolution of this sulfate-rich layer in Yellowknife Bay, or beyond, led to the pure sulfate veins observed in YKB. This scenario is analogous to similar processes identified at a terrestrial site in Triassic sediments with gypsum veins of the Mercia Mudstone Group in Watchet Bay, UK.
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