共 31 条
JunB Protects against Myeloid Malignancies by Limiting Hematopoietic Stem Cell Proliferation and Differentiation without Affecting Self-Renewal
被引:114
作者:

Santaguida, Marianne
论文数: 0 引用数: 0
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机构:
Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

Schepers, Koen
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

King, Bryan
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

Sabnis, Amit J.
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h-index: 0
机构:
Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

Forsberg, E. Camilla
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Santa Cruz, Inst Biol Stem Cells, Santa Cruz, CA 95064 USA Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

Attema, Joanne L.
论文数: 0 引用数: 0
h-index: 0
机构:
Lund Univ, Inst Expt Med Sci, S-22184 Lund, Sweden Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

Braun, Benjamin S.
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h-index: 0
机构:
Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

Passegue, Emmanuelle
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA
机构:
[1] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
[3] Univ Calif Santa Cruz, Inst Biol Stem Cells, Santa Cruz, CA 95064 USA
[4] Lund Univ, Inst Expt Med Sci, S-22184 Lund, Sweden
来源:
关键词:
TGF-BETA;
GENE-EXPRESSION;
IN-VIVO;
LEUKEMIA;
MAINTENANCE;
NOTCH;
PROGENITORS;
P16(INK4A);
NICHES;
D O I:
10.1016/j.ccr.2009.02.016
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Loss of the JunB/AP-1 transcription factor induces a myeloproliferative disease (MPD) arising from the hematopoietic stem cell (HSC) compartment. Here, we show that junB inactivation deregulates the cell-cycle machinery and increases the proliferation of long-term repopulating HSCs (LT-HSCs) without impairing their self-renewal or regenerative potential in vivo. We found that JunB loss destabilizes a complex network of genes and pathways that normally limit myeloid differentiation, leading to impaired responsiveness to both Notch and TGF-beta signaling due in part to transcriptional deregulation of the Hes1 gene. These results demonstrate that LT-HSC proliferation and differentiation are uncoupled from self-renewal and establish some of the mechanisms by which JunB normally limits the production of myeloid progenitors, hence preventing initiation of myeloid malignancies.
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收藏
页码:341 / 352
页数:12
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