共 42 条
RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity
被引:56
作者:

Cellot, Sonia
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada
Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada
Ste Justine Hosp, Div Hematol, Montreal, PQ, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Hope, Kristin J.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Chagraoui, Jalila
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Sauvageau, Martin
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Deneault, Eric
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

MacRae, Tara
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Mayotte, Nadine
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Wilhelm, Brian T.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Landry, Josette R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Ting, Stephen B.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada
Monash Univ, Melbourne, Vic 3004, Australia Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Krosl, Jana
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Humphries, Keith
论文数: 0 引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
Univ British Columbia, Dept Med, Vancouver, BC, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Thompson, Alexander
论文数: 0 引用数: 0
h-index: 0
机构:
Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT7 1NN, Antrim, North Ireland Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

Sauvageau, Guy
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada
Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada
Hop Maison Neuve Rosemont, Div Hematol, Montreal, PQ H1T 2M4, Canada
Hop Maison Neuve Rosemont, Leukemia Cell Bank Quebec, Montreal, PQ H1T 2M4, Canada Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada
机构:
[1] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada
[2] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada
[3] Ste Justine Hosp, Div Hematol, Montreal, PQ, Canada
[4] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[5] Univ British Columbia, Dept Med, Vancouver, BC, Canada
[6] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT7 1NN, Antrim, North Ireland
[7] Hop Maison Neuve Rosemont, Div Hematol, Montreal, PQ H1T 2M4, Canada
[8] Hop Maison Neuve Rosemont, Leukemia Cell Bank Quebec, Montreal, PQ H1T 2M4, Canada
[9] Monash Univ, Melbourne, Vic 3004, Australia
来源:
基金:
英国医学研究理事会;
关键词:
HEMATOPOIETIC STEM-CELLS;
OXIDATIVE DEMETHYLATION;
SELF-RENEWAL;
IN-VITRO;
PROLIFERATION;
POLYCOMB;
GENES;
CONTRIBUTES;
REPRESSION;
LEVEL;
D O I:
10.1182/blood-2013-04-496281
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Histone methylation is a dynamic and reversible process proposed to directly impact on stem cell fate. The Jumonji (JmjC) domain-containing family of demethylases comprises 27 members that target mono-, di-, and trimethylated lysine residues of histone (or nonhistone) proteins. To evaluate their role in regulation of hematopoietic stem cell (HSC) behavior, we performed an in vivo RNAi-based functional screen and demonstrated that Jarid1b and Jhdm1f play opposing roles in regulation of HSC activity. Decrease in Jarid1b levels correlated with an in vitro expansion of HSCs with preserved long-term in vivo lymphomyeloid differentiation potential. Through RNA sequencing analysis, Jarid1b knockdown was associated with increased expression levels of several HSC regulators (Hoxa7, Hoxa9, Hoxa10, Hes1, Gata2) and reduced levels of differentiation-associated genes. shRNA against Jhdmlf, in contrast, impaired hematopoietic reconstitution of bone marrow cells. Together, our studies identified Jarid1b as a negative regulator of HSC activity and Jhdmlf as a positive regulator of HSC activity.
引用
收藏
页码:1545 / 1555
页数:11
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h-index: 0
机构:
Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA