GLP-1 agonists are potent glucose-lowering agents, however, their effect on adolescent organisms needs to be clarified
Effects of the glucagon-like peptide-1 receptor agonist liraglutide in juvenile transgenic pigs modeling a pre-diabetic condition.
Age, Specimen part, Treatment
View SamplesThe translocation t(10,11)(p13;q14) resulting in the formation of the CALM/AF10 fusion gene is involved in various hematological malignancies including acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and malignant lymphoma and is usually associated with poor prognosis. We established a knock-in mouse model allowing tissue-specific CALM/AF10 expression from the Rosa26 locus using a loxP-STOP-loxP cassette to study leukemic transformation by the CALM/AF10 fusion protein during hematopoiesis. vav-Cre induced pan-hematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Leukemias were either myeloid or had myeloid feature and showed expression of the B cell marker B220. Gene expression profiling of leukemic bone marrow cells revealed the overexpression of Hoxa cluster genes and the Hox co-factor Meis1. The long latency to leukemia development suggested that additional, collaborative genetic lesions are required. We identified an average of 2 to 3 additional mutations per leukemia using whole-exome sequencing. When CALM/AF10 was expressed in the B lymphoid compartment using mb1-Cre or CD19-Cre inducer lines no leukemia development was observed. Our results indicate that CALM/AF10 needs to be expressed from the stem or early progenitor cell stage onward to permit the acquisition of additional mutations required for leukemic transformation.
The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models.
Disease
View SamplesMast cells originate from the bone marrow and develop into c-kit+ FcRI+ cells. As both mast cell progenitors and mature mast cells express these cell surface markers, ways validated to distinguish between the two maturation forms with flow cytometry have been lacking.
Distinguishing Mast Cell Progenitors from Mature Mast Cells in Mice.
Specimen part, Disease
View SamplesDifferentiation of haematopoietic stem cells followsa hierarchical program of transcription-factor regulated events. Early myeloid cell differentiation is dependent on PU.1 and CEBPA (CCAAT/enhancer binding protein alpha), late myeloid differentiation is orchestrated by CEBPE (CCAAT/enhancer binding protein epsilon). The influence of SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodelling factors as novel master regulators of haematopoietic differentiation is only beginning to be explored. Here, we identified three homozygous loss-of-function mutations in SMARCD2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2), a member of the SWI/SNF complex, in three unrelated pedigrees. We find that SMARCD2-deficient hematopoiesis results in dysfunctional neutrophil granulocytes, characterized by specific granule deficiency, myelodysplasia, and an excess of blast cells. We can show that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells in mice and zebra fish. In vitro SMARCD2 interacts with the transcription factor CEBPE. Furthermore, we find that SMARCD2 controls expression of neutrophil proteins stored in specific granules and leads to transcriptional and chromatin changes in AML cells. Hence, we identify SMARCD2 as a key factor controlling myelopoiesis and as a potential tumour suppressor in leukemia. Overall design: We analyzed CD45.2+ Lin- Mac+/low Sca1+ cKit+ (LSK) cells from Smarcd2 wild-type, heterozygous and mutant foetal livers in at least 5 replicates Additionally, we analysed three different progenitor populations from Smarcd2 wild-type and homozygous knock-out foetal livers: CD45+Lin-Sca-1-CD177+CD34lowCD16/32 (FCGR)low(MEP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)int (CMP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)high (GMP)
Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes.
Sex, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global analysis of the relationship between JIL-1 kinase and transcription.
Specimen part, Cell line
View SamplesProfiling of changes in steady state RNA levels upon RNAi-mediated knockdown of the chromosomal kinase JIL-1 in Drosophila S2 cells.
Global analysis of the relationship between JIL-1 kinase and transcription.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Specimen part
View SamplesTo investgate the role of EBF1 in human adipocyte, we performed global expression profiling in human adipocytes transfected with siRNA targeting EBF1.
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sex, Age, Specimen part, Subject
View SamplesWe used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Age, Specimen part
View Samples