Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 548-558 |
| Number of pages | 11 |
| Journal | Cell Stem Cell |
| Volume | 4 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 5 2009 |
| Externally published | Yes |
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Keywords
- STEMCELL
ASJC Scopus subject areas
- Cell Biology
- Molecular Medicine
- Genetics
Cite this
Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function. / Gao, Jie; Graves, Stephanie; Koch, Ute; Liu, Suqing; Jankovic, Vladimir; Buonamici, Silvia; El Andaloussi, Abdeljabar; Nimer, Stephen D; Kee, Barbara L.; Taichman, Russell; Radtke, Freddy; Aifantis, Iannis.
In: Cell Stem Cell, Vol. 4, No. 6, 05.06.2009, p. 548-558.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function
AU - Gao, Jie
AU - Graves, Stephanie
AU - Koch, Ute
AU - Liu, Suqing
AU - Jankovic, Vladimir
AU - Buonamici, Silvia
AU - El Andaloussi, Abdeljabar
AU - Nimer, Stephen D
AU - Kee, Barbara L.
AU - Taichman, Russell
AU - Radtke, Freddy
AU - Aifantis, Iannis
PY - 2009/6/5
Y1 - 2009/6/5
N2 - 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.
AB - 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.
KW - STEMCELL
UR - http://www.scopus.com/inward/record.url?scp=66049102512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66049102512&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2009.03.015
DO - 10.1016/j.stem.2009.03.015
M3 - Article
C2 - 19497283
AN - SCOPUS:66049102512
VL - 4
SP - 548
EP - 558
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 6
ER -