title: Posttranscriptional regulation of c-Myc expression in adult murine HSCs during homeostasis and interferon-α-induced stress response.
abstract: Previous studies have established pivotal roles for c-Myc and its homolog N-Myc in hematopoietic stem cell (HSC) maintenance and niche-dependent differentiation. However, it remains largely unclear how c-Myc expression is regulated in this context. Here, we show that HSCs and more committed progenitors express similar levels of c-myc transcripts. Using knock-in mice expressing a functional enhanced green fluorescent protein-c-Myc fusion protein under control of the endogenous c-myc locus, c-Myc protein levels were assessed. Although HSCs express low levels of c-Myc protein, its expression increases steadily during progenitor differentiation. Thus, mRNA and protein expression patterns differ significantly in stem/progenitor cells, suggesting that c-Myc expression is largely controlled posttranscriptionally. Moreover, interferon-α exposure, which activates dormant HSCs, strongly induces c-Myc expression at the protein level but not at the transcript level. This posttranscriptional mechanism of c-Myc regulation provides the blood system with a rapid way to adjust c-Myc expression according to demand during hematopoietic stress.
authors.affiliation: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; and.
authors.forename: Armin
authors.initials: A
authors.lastname: Ehninger
authors.affiliation: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; and.
authors.forename: Tobias
authors.initials: T
authors.lastname: Boch
authors.affiliation: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; and.
authors.forename: Hannah
authors.initials: H
authors.lastname: Uckelmann
authors.affiliation: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; and.
authors.forename: Marieke A
authors.initials: MA
authors.lastname: Essers
authors.affiliation: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; and.
authors.forename: Katja
authors.initials: K
authors.lastname: Müdder
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Barry P
authors.initials: BP
authors.lastname: Sleckman
authors.affiliation: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects* / Q000235:genetics; D016898:Interferon-alpha / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D016898:Interferon-alpha; D016271:Proto-Oncogene Proteins c-myc; D049452:Green Fluorescent Proteins