Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function

Jie Gao, Stephanie Graves, Ute Koch, Suqing Liu, Vladimir Jankovic, Silvia Buonamici, Abdeljabar El Andaloussi, Stephen D. Nimer, Barbara L. Kee, Russell Taichman, Freddy Radtke, Iannis Aifantis

Research output: Contribution to journalArticle

130 Scopus citations

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 languageEnglish (US)
Pages (from-to)548-558
Number of pages11
JournalCell Stem Cell
Volume4
Issue number6
DOIs
StatePublished - Jun 5 2009

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Keywords

  • STEMCELL

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Gao, J., Graves, S., Koch, U., Liu, S., Jankovic, V., Buonamici, S., El Andaloussi, A., Nimer, S. D., Kee, B. L., Taichman, R., Radtke, F., & Aifantis, I. (2009). Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function. Cell Stem Cell, 4(6), 548-558. https://doi.org/10.1016/j.stem.2009.03.015