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ERG promotes the ma...
ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.
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Knudsen, Kasper Jermiin (author)
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Rehn, Matilda (author)
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Hasemann, Marie Sigurd (author)
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Rapin, Nicolas (author)
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Bagger, Frederik Otzen (author)
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Ohlsson, Ewa (author)
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Willer, Anton (author)
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Frank, Anne-Katrine (author)
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Søndergaard, Elisabeth (author)
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Jendholm, Johan (author)
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Thorén, Lina (author)
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Lee, Julie (author)
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- Rak, Justyna (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Theilgaard-Moench, Kim (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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Porse, Bo Torben (author)
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(creator_code:org_t)
- 2015-09-18
- 2015
- English.
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In: Genes & Development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 29:18, s. 1915-1929
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Abstract
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- The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors that serve to restrict HSC differentiation. In the present work, we identify ETS (E-twenty-six)-related gene (ERG) as a critical factor protecting HSCs from differentiation. Specifically, loss of Erg accelerates HSC differentiation by >20-fold, thus leading to rapid depletion of immunophenotypic and functional HSCs. Molecularly, we could demonstrate that ERG, in addition to promoting the expression of HSC self-renewal genes, also represses a group of MYC targets, thereby explaining why Erg loss closely mimics Myc overexpression. Consistently, the BET domain inhibitor CPI-203, known to repress Myc expression, confers a partial phenotypic rescue. In summary, ERG plays a critical role in coordinating the balance between self-renewal and differentiation of HSCs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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Knudsen, Kasper ...
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Rehn, Matilda
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Hasemann, Marie ...
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Rapin, Nicolas
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Bagger, Frederik ...
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Ohlsson, Ewa
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show more...
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Willer, Anton
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Frank, Anne-Katr ...
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Søndergaard, Eli ...
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Jendholm, Johan
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Thorén, Lina
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Lee, Julie
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Rak, Justyna
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Theilgaard-Moenc ...
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Porse, Bo Torben
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- MEDICAL AND HEALTH SCIENCES
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Lund University