Transcriptomics

Dataset Information

28

Hematopoietic Stem Cell Differentiation Regulated by a Single Ubiquitin Ligase: Substrate Complex


ABSTRACT: Hematopoietic 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. Overall design: 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.

REANALYSED by: GSE119128

INSTRUMENT(S): [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array

ORGANISM(S): Mus musculus  

SUBMITTER: Jiri Zavadil  

PROVIDER: GSE19502 | GEO | 2010-03-01

SECONDARY ACCESSION(S): PRJNA122423

REPOSITORIES: GEO

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