We used microarrays to reveal the global expression profiles of young and old whole lateral ventricle choroid plexus tissue.
Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells.
Sex, Specimen part
View SamplesStem cells (SC) exhibit a unique capacity for self-renewal in an undifferentiated state. It is unclear whether the self-renewal of pluripotent embryonic SC (ESC) and of tissue-specific adult SC such as hematopoietic SC (HSC) is controlled by common mechanisms. The deletion of transcription factor Zfx impaired the self-renewal but not the differentiation capacity of murine ESC; conversely, Zfx overexpression facilitated ESC self-renewal by opposing differentiation. Furthermore, Zfx deletion abolished the maintenance of adult bone marrow HSC, but did not affect erythromyeloid progenitors or fetal HSC. In both ESC and HSC, Zfx activated a common set of direct target genes. In addition, the loss of Zfx resulted in the induction of immediate-early and/or stress-inducible genes in both SC types but not in their differentiated progeny. These studies identify the first shared transcriptional regulator of ESC and HSC, suggesting a common molecular basis of self-renewal in embryonic and adult SC.
Zfx controls the self-renewal of embryonic and hematopoietic stem cells.
No sample metadata fields
View SamplesRNA was purified from GFAP::GFP+CD133+ and GFAP::GFP+CD133+EGFR+ cells isolated from the adult mouse V-SVZ niche (GFAP::GFP mice, Jackson Mice Stock number 003257)
Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcriptional network for mesenchymal transformation of brain tumours.
Time
View SamplesUsing a novel combination of cellular-network reverse-engineering algorithms and experimental validation assays, we identified a transcriptional module, including six transcription factors that synergistically regulates the mesenchymal signature of malignant glioma. This is a poorly understood molecular phenotype, never observed in normal neural tissue. It represents the hallmark of tumor aggressiveness in high-grade glioma, and its upstream regulation is so far unknown. Overall, the newly discovered transcriptional module regulates >74% of the signature genes, while two of its transcription factors (C/EBP and Stat3) display features of initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBP and Stat3 is sufficient to reprogram neural stem cells along the aberrant mesenchymal lineage, while simultaneously suppressing differentiation along the default neural lineages (neuronal and glial). Conversely, silencing the two transcription factors in human glioma cell lines and glioblastoma-derived tumor initiating cells leads to collapse of the mesenchymal signature with corresponding loss of tumor aggressiveness in vitro and in immunodeficient mice after intracranial injection. In human tumor samples, combined expression of C/EBP and Stat3 correlates with mesenchymal differentiation of primary glioma and is a predictor of poor clinical outcome. Taken together, these results reveal that activation of a small regulatory module inferred from the accurate reconstruction of transcriptional networks is necessary and sufficient to initiate and maintain an aberrant phenotypic state in eukaryotic cells.
The transcriptional network for mesenchymal transformation of brain tumours.
Time
View SamplesUsing a novel combination of cellular-network reverse-engineering algorithms and experimental validation assays, we identified a transcriptional module, including six transcription factors that synergistically regulates the mesenchymal signature of malignant glioma. This is a poorly understood molecular phenotype, never observed in normal neural tissue. It represents the hallmark of tumor aggressiveness in high-grade glioma, and its upstream regulation is so far unknown. Overall, the newly discovered transcriptional module regulates >74% of the signature genes, while two of its transcription factors (C/EBP and Stat3) display features of initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBP and Stat3 is sufficient to reprogram neural stem cells along the aberrant mesenchymal lineage, while simultaneously suppressing differentiation along the default neural lineages (neuronal and glial). Conversely, silencing the two transcription factors in human glioma cell lines and glioblastoma-derived tumor initiating cells leads to collapse of the mesenchymal signature with corresponding loss of tumor aggressiveness in vitro and in immunodeficient mice after intracranial injection. In human tumor samples, combined expression of C/EBP and Stat3 correlates with mesenchymal differentiation of primary glioma and is a predictor of poor clinical outcome. Taken together, these results reveal that activation of a small regulatory module, inferred from the accurate reconstruction of transcriptional networks, is necessary and sufficient to initiate and maintain an aberrant phenotypic state in eukaryotic cells.
The transcriptional network for mesenchymal transformation of brain tumours.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
Specimen part
View SamplesThe transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs.
Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
Specimen part
View SamplesThe transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs.
Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
Specimen part
View SamplesThe forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival.
Differentiation of CD8 memory T cells depends on Foxo1.
Specimen part
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