Self-renewal and differentiation of pluripotent murine embryonic stem cells (ESCs) is regulated by extrinsic signaling pathways. It is less clear whether cellular metabolism instructs developmental progression. In an unbiased genome-wide CRISPR/Cas9 screen, we identified components of a conserved amino-acid-sensing pathway as critical drivers of ESC differentiation. Functional analysis revealed that lysosome activity, the Ragulator protein complex, and the tumor-suppressor protein Folliculin enable the Rag GTPases C and D to bind and seclude the bHLH transcription factor Tfe3 in the cytoplasm. In contrast, ectopic nuclear Tfe3 represses specific developmental and metabolic transcriptional programs that are associated with peri-implantation development. We show differentiation-specific and non-canonical regulation of Rag GTPase in ESCs and, importantly, identify point mutations in a Tfe3 domain required for cytoplasmic inactivation as potentially causal for a human developmental disorder. Our work reveals an instructive and biomedically relevant role of metabolic signaling in licensing embryonic cell fate transitions.
Pubmed ID: 30595499 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsThe goal of the project is to discover novel genes and mechanisms contributing to heart, lung and blood disorders by pioneering the application of next-generation sequencing of the protein coding regions of the human genome across diverse, richly-phenotyped populations and to share these datasets and findings with the scientific community to extend and enrich the diagnosis, management and treatment of heart, lung and blood disorders. The groups participating and collaborating in the NHLBI GO ESP include: Seattle GO - University of Washington, Seattle, WA Broad GO - Broad Institute of MIT and Harvard, Cambridge, MA WHISP GO - Ohio State University Medical Center, Columbus, OH Lung GO - University of Washington, Seattle, WA WashU GO - Washington University, St. Louis, MO Heart GO - University of Virginia Health System, Charlottesville, VA ChargeS GO - University of Texas Health Sciences Center at Houston
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 9, 2023. An aggregated data platform for genome sequencing data created by a coalition of investigators seeking to aggregate and harmonize exome sequencing data from a variety of large-scale sequencing projects, and to make summary data available for the wider scientific community. The data set provided on this website spans 61,486 unrelated individuals sequenced as part of various disease-specific and population genetic studies. They have removed individuals affected by severe pediatric disease, so this data set should serve as a useful reference set of allele frequencies for severe disease studies. All of the raw data from these projects have been reprocessed through the same pipeline, and jointly variant-called to increase consistency across projects. They ask that you not publish global (genome-wide) analyses of these data until after the ExAC flagship paper has been published, estimated to be in early 2015. If you''re uncertain which category your analyses fall into, please email them. The aggregation and release of summary data from the exomes collected by the Exome Aggregation Consortium has been approved by the Partners IRB (protocol 2013P001477, Genomic approaches to gene discovery in rare neuromuscular diseases).
View all literature mentionsThis monoclonal targets RagB (D18F3) Rabbit mAb
View all literature mentionsThis polyclonal targets p70 S6 Kinase
View all literature mentionsThis unknown targets Human TFE3
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein
View all literature mentionsThis polyclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)
View all literature mentionsThis monoclonal targets GAPDH antibody produced in mouse
View all literature mentionsThis monoclonal targets LAMTOR1/C11orf59 (D11H6) XP Rabbit mAb
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets 4E-BP1
View all literature mentionsThis monoclonal targets RagC
View all literature mentionsThis monoclonal targets TSC2
View all literature mentionsThis polyclonal targets Phospho-p70 S6 Kinase (Thr389)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets RagB (D18F3) Rabbit mAb
View all literature mentionsThis monoclonal targets GAPDH antibody produced in mouse
View all literature mentionsThis monoclonal targets LAMTOR1/C11orf59 (D11H6) XP Rabbit mAb
View all literature mentionsThis monoclonal targets RagC
View all literature mentionsThis polyclonal targets p70 S6 Kinase
View all literature mentionsThis polyclonal targets 4E-BP1
View all literature mentionsThis monoclonal targets TSC2
View all literature mentionsThis unknown targets Human TFE3
View all literature mentionsThis polyclonal targets Phospho-p70 S6 Kinase (Thr389)
View all literature mentionsThis polyclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein
View all literature mentions