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ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

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@article{e1decf6b91f5417b9458f6f09e91f99d,
title = "ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation",
abstract = "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.",
author = "Knudsen, {Kasper Jermiin} and Rehn, {Matilda Carolina} and Hasemann, {Marie Sigurd} and Nicolas Rapin and Bagger, {Frederik Otzen} and Ewa Ohlsson and Anton Willer and Frank, {Anne Katrine} and Elisabeth S{\o}ndergaard and Johan Jendholm and Lina Thor{\'e}n and Julie Lee and Justyna Rak and Kim Theilgaard-M{\"o}nch and Porse, {Bo Torben}",
note = "{\circledC} 2015 Knudsen et al.; Published by Cold Spring Harbor Laboratory Press.",
year = "2015",
month = "9",
day = "15",
doi = "10.1101/gad.268409.115",
language = "English",
volume = "29",
pages = "1915--29",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press Publications Department",
number = "18",

}

RIS

TY - JOUR

T1 - ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

AU - Knudsen, Kasper Jermiin

AU - Rehn, Matilda Carolina

AU - Hasemann, Marie Sigurd

AU - Rapin, Nicolas

AU - Bagger, Frederik Otzen

AU - Ohlsson, Ewa

AU - Willer, Anton

AU - Frank, Anne Katrine

AU - Søndergaard, Elisabeth

AU - Jendholm, Johan

AU - Thorén, Lina

AU - Lee, Julie

AU - Rak, Justyna

AU - Theilgaard-Mönch, Kim

AU - Porse, Bo Torben

N1 - © 2015 Knudsen et al.; Published by Cold Spring Harbor Laboratory Press.

PY - 2015/9/15

Y1 - 2015/9/15

N2 - 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.

AB - 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.

U2 - 10.1101/gad.268409.115

DO - 10.1101/gad.268409.115

M3 - Journal article

VL - 29

SP - 1915

EP - 1929

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 18

ER -

ID: 45654426