Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function

被引：180

作者：

Gao, Jie ^{[1
,2
,3
]}

Graves, Stephanie ^{[4
]}

Koch, Ute ^{[5
]}

Liu, Suqing ^{[1
,2
,3
]}

Jankovic, Vladimir ^{[6
]}

Buonamici, Silvia ^{[1
,2
,3
]}

El Andaloussi, Abdeljabar ^{[7
]}

Nimer, Stephen D. ^{[6
]}

Kee, Barbara L. ^{[4
]}

Taichman, Russell ^{[8
]}

Radtke, Freddy ^{[5
]}

Aifantis, Iannis ^{[1
,2
,3
]}

机构：

[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[2] NYU, Sch Med, Inst Canc, New York, NY 10016 USA

[3] NYU, Sch Med, Helen & Martin S Kimmel Stem Cell Ctr, New York, NY 10016 USA

[4] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA

[5] Swiss Inst Expt Canc Res, Ecole Polytech Fed Lausanne, CH-1066 Epalinges, Switzerland

[6] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, Sloan Kettering Inst, New York, NY 10021 USA

[7] Univ Sherbrooke, Fac Med, Sherbrooke, PQ J1K 2R1, Canada

[8] Univ Michigan, Dept Periodont & Oral Med, Sch Dent, Ann Arbor, MI 48109 USA

来源：

CELL STEM CELL | 2009年 / 4卷 / 06期

基金：

瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

SELF-RENEWAL; GENE-EXPRESSION; MAINTENANCE; REVEALS; NOTCH; SHH; COMMITMENT; ACTIVATION; MUTATIONS; PATHWAY;

D O I：

10.1016/j.stem.2009.03.015

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

The Hedgehog (Hh) signaling pathway is a developmentally conserved regulator of stem cell function. Several reports suggested that Hh signaling is an important regulator of hematopoietic stem cell (HSC) maintenance and differentiation. Here we test this hypothesis in vivo using both gain- and loss-of-function Hh genetic models. Surprisingly, our studies demonstrate that conditional Smoothened (Smo) deletion or overactivation has no significant effects on adult HSC self-renewal and function. Moreover, they indicate a lack of synergism between the Notch and Hh pathways in HSC function, as compound RBPJ and Smo deficiency does not affect hematopoiesis. In agreement with this notion, detailed genome-wide transcriptome analysis reveals that silencing of Hh signaling does not significantly alter the HSC-specific gene expression "signature." Our studies demonstrate that the Hh signaling pathway is dispensable for adult HSC function and suggest that Hh inhibition on leukemia-initiating cell maintenance can be targeted in future clinical trials.

引用

页码：548 / 558

页数：11

共 45 条

[1]

The hematopoietic stem cell in its place [J].