0000000000520229

AUTHOR

Svetlana Ohngemach

showing 4 related works from this author

Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mous…

2013

The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was foll…

cancer stem cellsCancer stem cells; Core binding factor acute myeloid leukaemia; Preclinical mouse model; Therapy target validation; Whole transcriptome sequencingMyeloidtherapy target validationOncogene Proteins FusionCloseupsBiologyGranulocyte-Macrophage Progenitor CellsTranslocation Geneticwhole transcriptome sequencingImmunophenotypingMiceGranulocyte-Macrophage Progenitor CellsCancer stem cellhemic and lymphatic diseasesmedicineAML1-ETOAnimalsCell Lineageacute myeloid leukaemiaLymphopoiesisProgenitor cellt(8;21)Research Articlespreclinical mouse modelGeneticsRegulation of gene expressionAntibiotics AntineoplasticSequence Analysis RNAcore binding factor acute myeloid leukaemiainducible mouse-modelHematopoietic Stem CellsMice Inbred C57BLDisease Models AnimalLeukemia Myeloid AcuteHaematopoiesisPhenotypemedicine.anatomical_structureGene Expression RegulationDoxorubicinCancer researchNeoplastic Stem CellsMolecular MedicineStem cell
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The Wnt/beta-Catenin Pathway Attenuates Experimental Allergic Airway Disease

2014

Abstract Signaling via the Wnt/β-catenin pathway plays crucial roles in embryogenesis and homeostasis of adult tissues. In the lung, the canonical Wnt/β-catenin pathway has been implicated in remodeling processes, development of emphysema, and fibrosis. However, its relevance for the modulation of allergic responses in the lung remains unclear. Using genetically modified mice with lung-specific inducible (doxycycline) Wnt-1 expression (CCSP-rtTA × tetO-Wnt1), the impact of Wnt on the development of allergic airway disease was analyzed. Overexpression of Wnt during the allergen challenge phase attenuated the development of airway inflammation in an acute model, as well as in a more therapeut…

OvalbuminTransgeneT cellT-LymphocytesImmunologyMice TransgenicWnt1 ProteinMiceAdjuvants ImmunologicFibrosisCell MovementmedicineRespiratory HypersensitivityImmunology and AllergyAnimalsLungCells Culturedbeta CateninMice Inbred BALB CLungbusiness.industryWnt signaling pathwayDendritic Cellsrespiratory systemmedicine.diseaseFlow CytometryIn vitroCoculture Techniquesrespiratory tract diseasesMice Inbred C57BLmedicine.anatomical_structureCateninDoxycyclineImmunologyCytokinesbusinessLithium ChlorideHomeostasisSignal Transduction
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Inducible knockdown of procollagen I protects mice from liver fibrosis and leads to dysregulated matrix genes and attenuated inflammation.

2017

Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary liver cancer, which are the major causes of liver related morbidity and mortality. However, a (pro-)collagen type I specific therapy remains difficult and its therapeutic abrogation may incur unwanted side effects. We therefore designed tetracycline-regulated procollagen alpha1(I) short hairpin (sh)RNA expressing mice that permit a highly efficient inducible knockdown of the procollagen alpha1(I) gen…

0301 basic medicineGenetically modified mouseLiver CirrhosisPathologymedicine.medical_specialtyCirrhosisInflammationMice TransgenicCollagen Type ISmall hairpin RNAExtracellular matrix03 medical and health sciencesMiceFibrosismedicineAnimalsRNA Small InterferingMolecular BiologyCells CulturedGene knockdownExtracellular Matrix ProteinsChemistryMouse Embryonic Stem CellsFibroblastsmedicine.diseaseProcollagen peptidaseDisease Models Animal030104 developmental biologyGene Expression RegulationGene Knockdown TechniquesCancer researchmedicine.symptomProcollagenMatrix biology : journal of the International Society for Matrix Biology
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Tetracycline-controlled transgenic targeting from the SCL locus directs conditional expression to erythrocytes, megakaryocytes, granulocytes, and c-k…

2006

The stem cell leukemia gene SCL, also known as TAL-1, encodes a basic helix-loop-helix transcription factor expressed in erythroid, myeloid, megakaryocytic, and hematopoietic stem cells. To be able to make use of the unique tissue-restricted and spatio-temporal expression pattern of the SCL gene, we have generated a knock-in mouse line containing the tTA-2S tetracycline transactivator under the control of SCL regulatory elements. Analysis of this mouse using different tetracycline-dependent reporter strains demonstrated that switchable transgene expression was restricted to erythrocytes, megakaryocytes, granulocytes, and, importantly, to the c-kit-expressing and lineage-negative cell fracti…

MyeloidErythrocytesGenotypeTransgeneImmunologyMice TransgenicBiologyBiochemistryMiceMegakaryocyteGenes Reporterhemic and lymphatic diseasesProto-Oncogene ProteinsmedicineBasic Helix-Loop-Helix Transcription FactorsAnimalsT-Cell Acute Lymphocytic Leukemia Protein 1DNA PrimersRegulation of gene expressionReporter geneBase SequenceCell BiologyHematologyTetracyclineFlow CytometryMolecular biologyRecombinant ProteinsHematopoiesisHaematopoiesisProto-Oncogene Proteins c-kitmedicine.anatomical_structureGene Expression RegulationBone marrowStem cellMegakaryocytesGranulocytesBlood
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