ArrayExpress Uploader0mouse5930arrayexpress_sid6Hematopoietic stem cell (HSC) differentiation is regulated by cell-intrinsic and extrinsic cues. In addition to transcriptional...E-GEOD-19502/profile/8773/arrayexpressuploader04cellchromatingenomeproteinstem cellDec.12, 2014Falsehematopoietic-stem-cell-differentiation-regulatedE-GEOD-19502_A-AFFY-45Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate ComplexNov.11, 2014Hematopoietic stem cell (HSC) differentiation is regulated by cell-intrinsic and extrinsic cues. In addition to transcriptional regulation, post-translational regulation may also control HSC differentiation. To test this hypothesis, we visualized ubiquitin-regulated protein stability of a single transcription factor, c-Myc. The stability of c-Myc protein was instructive of HSC quiescence and c-Myc protein abundance was controlled by the ubiquitin ligase Fbw7. Fine changes in stability of c-Myc protein regulated the HSC “gene expression signature”. Using whole genome genomic approaches, we identified specific regulators of HSC function that are directly controlled by c-Myc binding, however adult HSCs and embryonic stem cells sense and interpret distinctly c-Myc regulated gene expression. These studies show a ubiquitin ligase–substrate pair can orchestrate the molecular program of HSC differentiation. Gene expression profiles from c-Myc-High and c-Myc-Low expressing Lineage negative, c-Kit and Sca1 positive (LSKs) were compared using genome wide mRNA expression profiling by Affymetrix genechip arrays (Mouse 430 2.0) and key targets were validated by chromatin immunoprecipitation experiments.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-19502http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-19502/samples/