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

127 Citations (Scopus)

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

Fingerprint

Adult Stem Cells
Hematopoietic Stem Cells
Maintenance
Genetic Models
Hematopoiesis
Gene Expression Profiling
Transcriptome
Cell Differentiation
Leukemia
Stem Cells
Clinical Trials
Genome

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., ... 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

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 journalArticle

Gao, J, Graves, S, Koch, U, Liu, S, Jankovic, V, Buonamici, S, El Andaloussi, A, Nimer, SD, Kee, BL, Taichman, R, Radtke, F & Aifantis, I 2009, 'Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function', Cell Stem Cell, vol. 4, no. 6, pp. 548-558. https://doi.org/10.1016/j.stem.2009.03.015
Gao J, Graves S, Koch U, Liu S, Jankovic V, Buonamici S et al. Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function. Cell Stem Cell. 2009 Jun 5;4(6):548-558. https://doi.org/10.1016/j.stem.2009.03.015
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. / Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function. In: Cell Stem Cell. 2009 ; Vol. 4, No. 6. pp. 548-558.
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