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 SamplesThe Myc proteins (N-, L- and c-Myc) are transcription factors involved in many biological functions such as regulation of cell proliferation, differentiation, metabolism and apoptosis. A large number of human cancers show enhanced expression of myc family proto-oncogenes as one of their hallmarks. These proteins contain a basic region/helix-loop-helix/leucine zipper (bHLHZip) domain that mediates DNA binding and heterodimerization with its partner Max (Myc/Max heterodimer). Among Myc proteins, c-Myc is the most widely expressed and relevant in primary B lymphocytes. Some reports have implied that c-Myc can perform some functions without Max in different cell contexts. However, the functional interplay in vivo between c-Myc and Max during B lymphocyte differentiation is not well-known. Here we show that c-Myc requires Max. However, key biological processes such as cell differentiation and DNA replication can initially progress without c-Myc/Max heterodimer in primary B lymphocytes. We found that B lymphocytes lacking Myc, Max or both showed upregulation of signalling pathways associated with the B cell receptor. Our data suggest that c-Myc/Max heterodimers are not essential for the initiation of certain biological processes in B lymphocytes. Rather, c-Myc/Max are necessary for fine-tuning the initial response in these cells after activation. Overall design: B cell mRNA profiles of 8-week old control (HET) Myc deficient (MycKO), Max deficient (MaxKO) and double deficient (DKO) mice were generated by deep sequencing, in duplicate, using a HiSeq2500 (Illumina.
Functional interplay between c-Myc and Max in B lymphocyte differentiation.
Age, Specimen part, Subject
View SamplesOur laboratory wanted to define the transcription profile of aged skeletal muscle. For this reason, we performed a triplicate microarray study on young (3 weeks) and aged (24 months) gatrocnemius muscle from wild-type C57B16 Mice
Transcriptional profiling of skeletal muscle reveals factors that are necessary to maintain satellite cell integrity during ageing.
Sex
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.
No sample metadata fields
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
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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
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