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

被引：68

作者：

Knudsen, Kasper Jermiin ^{[1
,2
,3
]}

Rehn, Matilda ^{[1
,2
,3
]}

Hasemann, Marie Sigurd ^{[1
,2
,3
]}

Rapin, Nicolas ^{[1
,2
,3
,4
]}

Bagger, Frederik Otzen ^{[1
,2
,3
,4
]}

Ohlsson, Ewa ^{[1
,2
,3
]}

Willer, Anton ^{[1
,2
,3
]}

Frank, Anne-Katrine ^{[1
,2
,3
]}

Sondergaard, Elisabeth ^{[1
,2
,3
]}

Jendholm, Johan ^{[1
,2
,3
]}

Thoren, Lina ^{[1
,2
,3
]}

Lee, Julie ^{[1
,2
,3
]}

Rak, Justyna ^{[5
]}

Theilgaard-Monch, Kim ^{[1
,2
,6
]}

Porse, Bo Torben ^{[1
,2
,3
]}

机构：

[1] Univ Copenhagen, Fac Hlth Sci, Rigshosp, Finsen Lab, DK-2200 Copenhagen N, Denmark

[2] Univ Copenhagen, Biotech Res & Innovat Ctr, DK-2200 Copenhagen N, Denmark

[3] Univ Copenhagen, Fac Hlth Sci, Danish Stem Cell Ctr DanStem, DK-2200 Copenhagen N, Denmark

[4] Univ Copenhagen, Fac Nat Sci, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen N, Denmark

[5] Lund Univ, Lund Stem Cell Ctr, Mol Med & Gene Therapy, SE-22184 Lund, Sweden

[6] Lund Univ, Skanes Univ Hosp, Dept Hematol, SE-22185 Lund, Sweden

来源：

GENES & DEVELOPMENT | 2015年 / 29卷 / 18期

关键词：

hematopoietic stem cell; ERG; MYC; differentiation; self-renewal; CPI-203; TRANSCRIPTION FACTOR ERG; ACUTE MYELOID-LEUKEMIA; GENOME-WIDE ANALYSIS; ETS-RELATED GENE; SELF-RENEWAL; HIGH EXPRESSION; OVEREXPRESSION; KNOCKOUT; PREDICTS; CANCER;

D O I：

10.1101/gad.268409.115

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1915 / 1929

页数：15

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