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Publication : Posttranscriptional regulation of c-Myc expression in adult murine HSCs during homeostasis and interferon-α-induced stress response.

First Author  Ehninger A Year  2014
Journal  Blood Volume  123
Issue  25 Pages  3909-13
PubMed ID  24795346 Mgi Jnum  J:211286
Mgi Id  MGI:5574400 Doi  10.1182/blood-2013-10-531038
Citation  Ehninger A, et al. (2014) Posttranscriptional regulation of c-Myc expression in adult murine HSCs during homeostasis and interferon-alpha-induced stress response. Blood 123(25):3909-13
abstractText  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-alpha 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.
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