@article{f667d753caae482b9e0daf081797116e,
title = "Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function",
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.",
keywords = "STEMCELL",
author = "Jie Gao and Stephanie Graves and Ute Koch and Suqing Liu and Vladimir Jankovic and Silvia Buonamici and {El Andaloussi}, Abdeljabar and Nimer, {Stephen D.} and Kee, {Barbara L.} and Russell Taichman and Freddy Radtke and Iannis Aifantis",
note = "Funding Information: We would like to thank Dr. A. McMahon for the Smo F/F animals, Dr. A. Joyner for Gli1 lacZ animals, Jiri Zavadil for advice on microarray analysis, Peter Lopez for excellent cell-sorting support, Drs. T. Reya and G. Gilliland for sharing unpublished observations, and C.W. Brains for constructive discussions. The Aifantis laboratory is supported by a generous donation from the Helen L. and Martin S. Kimmel Stem Cell Center, the National Institutes of Health (NIH) (R56AI070310, RO1CA105129, and RO1CA133379 to I.A.; RO1 DK52208 to S.D.N.; and CA099978 to B.L.K.), the American Cancer Society (RSG0806801 to I.A.), the Leukemia and Lymphoma Society (Scholar Award to I.A. and a SCOR Award to S.D.N.), the New York State Department of Health (CO23058), the Irma T. Hirchl Trust, and the E. Mallinckrodt Foundation (to I.A.). F.R. is supported by the Swiss National Science Foundation (F3100A0-119725) and the Swiss Cancer League (KLS-01840-02-2006). S.G. is supported by the Medical Student Training Program (MSTP) program of the University of Chicago. ",
year = "2009",
month = jun,
day = "5",
doi = "10.1016/j.stem.2009.03.015",
language = "English (US)",
volume = "4",
pages = "548--558",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "6",
}