Mechanisms controlling the proliferative activity of neural stem/progenitor cells (NSPCs) play a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of FASN in NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for FASN to fuel lipogenesis. Thus, we here identified a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.
Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis.
Specimen part
View SamplesMYC is a major oncogenic driver of Multiple Myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM. We provide proof-of-principle for therapeutic regulation of MYC through let-7 with an LNA-GapmeR containing a let-7b mimic in vivo, demonstrating that high levels of let-7 expression repress tumor growth by regulating MYC expression. These findings reveal a novel mechanism of therapeutic targeting of MYC through the LIN28B/let-7 axis in MM that may impact other MYC dependent cancers as well. Overall design: RNA sequencing of MOLP-8 cells transduced with lentiCRISPRv2 scrambled control or containing a sgRNA against LIN28B. Both control and LIN28B KO cells were sequenced in triplicate.
The LIN28B/let-7 axis is a novel therapeutic pathway in multiple myeloma.
No sample metadata fields
View SamplesDifferential expression of genes between Arabidopsis WRKY18/40 knock out and wild type plants, after 8 h post inoculation of powdery mildew pathogen.
Transcriptional reprogramming regulated by WRKY18 and WRKY40 facilitates powdery mildew infection of Arabidopsis.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
View SamplesArs2 is a component of the nuclear cap-binding complex that is required for cellular proliferation and contributes to microRNA biogenesis. Arrays were performed to determine the repertoire of genes that change following knock-down of Ars2. Knock-down of DGCR8 was also performed to determine which changes in Ars2 knock-down cells resulted from defects in microRNA expression.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
View SamplesIn vitro experiment of stimulation of monocyte-derived dendritic cells with Saccaromyces cerevisiae in exponential growth phase. This experiment was performed to verify the comparability of microarray
Using pathway signatures as means of identifying similarities among microarray experiments.
No sample metadata fields
View SamplesIn this study, we used conditional knockout and gene expression approaches to understand global molecular and transciptional changes due to ablation of each integrin subunit.
Functional Redundancy between β1 and β3 Integrin in Activating the IR/Akt/mTORC1 Signaling Axis to Promote ErbB2-Driven Breast Cancer.
Specimen part
View SamplesNumerous studies have described the altered expression and the causal role of miRNAs in human cancer. However, to date efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here, we find that Nucleolin (NCL), a major nucleolar protein, post-transcriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, causally involved in breast cancer initiation, progression and drug-resistance. We also show that NCL is commonly overexpressed in human breast tumors, and its expression correlates with that of NCL-dependent miRNAs. Finally, this study indicates that NCL-binding guanosine-rich aptamers affect the levels of NCL-dependent miRNAs and their target genes, reducing breast cancer cell aggressiveness, both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer.
In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.
Cell line
View SamplesWe used microarrays to detail the global program of gene expression underlying Parkinson's disease
A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.
No sample metadata fields
View SamplesMM1S cells have been cultured under normoxic and hypoxic conditions, and gene expression profiling has been performed using the Affymetrix Human Genome U133 Plus 2.0 array.
Metabolic signature identifies novel targets for drug resistance in multiple myeloma.
Cell line
View Samples