The intestinal epithelium is continuously renewed by a pool of intestinal stem cells expressing Lgr5. We show that deletion of the key autophagy gene Atg7 affects the survival of Lgr5+ intestinal stem cells. Mechanistically, this involves defective DNA repair, oxidative stress, and altered interactions with the microbiota. This study highlights the importance of autophagy in maintaining the integrity of intestinal stem cells.
Essential role for autophagy protein ATG7 in the maintenance of intestinal stem cell integrity.
Specimen part
View SamplesMicroarray gene expression (MAGE) signatures allow insights into the transcriptional processes of leukemias and may evolve as a molecular diagnostic test. Introduction of MAGE into clinical practice of leukemia diagnosis will require comprehensive assessment of variation due to the methodologies.
New data on robustness of gene expression signatures in leukemia: comparison of three distinct total RNA preparation procedures.
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View SamplesIdentification of relevant subgroups in childhood MDS patients by gene expression analysis and gene involve in progression into AML
Gene expression signatures of pediatric myelodysplastic syndromes are associated with risk of evolution into acute myeloid leukemia.
Specimen part, Disease
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Comparative analysis of resistant and susceptible macrophage gene expression response to Leishmania major parasite.
Specimen part
View SamplesWe analyzed the transcriptional signatures of mouse bone marrow-derived macrophages (BMDM) at different times after infection with promastigotes of the protozoan parasite Leishmania major.
Comparative analysis of resistant and susceptible macrophage gene expression response to Leishmania major parasite.
Specimen part
View SamplesTo characterize LICs in ALL irrespective of surface markers expression, we investigated leukemia initiating activities of cellular subfractions of patient-derived xenograft BCP-ALL cells sorted according to different cell cycle phases (i.e. G0/G1 and G2/M) followed by transplantation onto NOD/SCID mice. All cell fractions led to leukemia engraftment indicating LIC activity irrespective of cell cycle stage. Most importantly, cells isolated from G0/G1 cell cycle phases led to early leukemia engraftment in contrast to cells from late cell cycle (G2/M). To further characterize cells with different engraftment potential in vivo, we analyzed the gene expression profiles of early (G1b early) and late (G2/M) engrafting cells.
Leukemia reconstitution <i>in vivo</i> is driven by cells in early cell cycle and low metabolic state.
Specimen part
View SamplesWe analyzed the transcriptional signatures of mouse bone marrow-derived macrophages (BMDM) at different times after infection with promastigotes of the protozoan parasite Leishmania major.
Transcriptomic signature of Leishmania infected mice macrophages: a metabolic point of view.
Specimen part
View SamplesHIF-1 plays a crucial role in sustaining glioblastoma (GBM) cell growth and the maintenance of their undifferentiated phenotype. However, HIF-1 has been suggested to interplay with Wnt signaling components, thus activating a neuronal differentiation process in both GBM and normal brain. Here, we show that a -catenin/TCF1/HIF-1 complex directly controls the transcription of neuronal differentiation genes in hypoxia. Conversely, at higher oxygen levels, the increased expression of TCF4 exerts a transcriptional inhibitory function on the same genomic regions, thus counteracting differentiation. Moreover, we demonstrate the existence of a positive correlation between HIF-1, TCF1 and neuronal phenotype in GBM tumors, accompanied by the over-expression of several Wnt signaling components, finally impacting on patient prognosis. In conclusion, we unveil a mechanism by which TCF1 and HIF-1 induce a reminiscent neuronal differentiation of hypoxic GBM cells, which is hampered, in normoxia, by high levels of TCF4, thus de facto sustaining cell aggressiveness.
HIF-1α/Wnt signaling-dependent control of gene transcription regulates neuronal differentiation of glioblastoma stem cells.
Specimen part
View SamplesGene expression analysis identified a specific signature of differentially expressed genes discriminating good and poor responders in JMML patients.
Gene expression-based classification as an independent predictor of clinical outcome in juvenile myelomonocytic leukemia.
Specimen part, Disease
View SamplesWe demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) against MLL-rearranged ALL using xenograft mouse models of MLL-rearranged ALL cell lines and primary patient cells. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed the anti-leukaemic activity in MLL-rearranged ALL to involve depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex.
The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis.
Treatment
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