This SuperSeries is composed of the SubSeries listed below.
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Specimen part
View SamplesDifferentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different transcription factors (TFs). A disturbed function of TFs can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Growth Factor Independence 1b (Gfi1b) is a repressing TF with a key role in quiescence of HSCs and emergence and maturation of erythrocytes and platelets. Here, we show that low expression of GFI1B in blast cells is associated with inferior prognosis of MDS and AML patients. Using mouse models with either reduced expression or conditional deletion of Gfi1b, crossed with a mouse model reflecting human MDS or AML, we demonstrate that AML development was accelerated with heterozygous loss of Gfi1b, and latency was further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b significantly enhanced stemness of leukemic cells with upregulation of genes fundamentally involved in leukemia development. On a molecular level, we found that loss of Gfi1b not only increased the levels of reactive oxygen species (ROS) but also induced gene expression changes of key AML pathways such as the p38/AKT pathway. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS/AML development.
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Specimen part
View SamplesFundamental research and drug development for personalized medicine necessitates cell cultures from defined genetic backgrounds. However, providing sufficient numbers of authentic cells from individuals poses a challenge. Here, we present a new strategy for rapid cell expansion that overcomes current limitations. Using a small gene library, we expanded primary cells from different tissues, donors and species. Cell type specific regimens that allow the reproducible creation of cell lines were identified. In depth characterization of a series of endothelial and hepatocytic cell lines confirmed phenotypic stability and functionality. Applying this technology enables rapid, efficient and reliable production of unlimited numbers of personalized cells. As such, these cell systems support mechanistic studies, epidemiological research and tailored drug development.
Expansion of functional personalized cells with specific transgene combinations.
Specimen part
View SamplesTranscriptional responses to stimuli are regulated by tuning rates of transcript production and degradation. Here we show that stimulation-induced changes in transcript production and degradation rates can be inferred from simultaneously measured precursor mRNA (pre-mRNA) and mature mRNA profiles. Our studies on the transcriptome-wide responses to extracellular stimuli in different cellular model systems revealed hitherto unanticipated dynamics of transcript production and degradation rates. Intriguingly, genes with similar mRNA profiles often exhibit marked differences in the amplitude and onset of their production. Moreover, we identify a group of genes, which take advantage of the unexpectedly large dynamic range of production rates to expedite their induction by a transient production overshoot. These findings provide an unprecedented quantitative view on processes governing transcriptional responses, and may have broad implications for understanding their regulation at the transcriptional and post-transcriptional levels.
Coupled pre-mRNA and mRNA dynamics unveil operational strategies underlying transcriptional responses to stimuli.
Cell line, Treatment
View SamplesMammary epithelial cells MCF10A and HER2 overexpressing MCF10A cells were grown on matrigel in the absence or presence of epidermal growth factor. Cells were lysed and RNA was collected at 1.5,3,5,7,9 days.
Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling.
Cell line, Treatment
View SamplesLow-dose epirubicin at non-cytotoxic doses down regulated NLRP3 inflammasome components and reduced the release of proinflammatory cytokines.
Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines.
Cell line
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