Hedgehog signaling is dispensable for adult hematopoietic stem cell function Journal Article
| Authors: | 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. |
| Article 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. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; leukemia; gene deletion; fluorouracil; nonhuman; animal cell; mouse; animals; mice; cell function; gene expression; gene expression profiling; sonic hedgehog protein; animal experiment; animal model; hedgehog proteins; notch receptor; in vivo study; adult stem cells; cell differentiation; mice, inbred strains; genome analysis; gene activation; nucleotide sequence; leukemia cell; receptors, notch; stemcell; hematopoietic stem cells; hematopoiesis; cell regeneration; hematopoietic stem cell; gene silencing; homeostasis; bone marrow transplantation; erinaceidae; genetic model; smoothened protein; transcriptome; adult stem cell; t cell leukemia; receptors, g-protein-coupled |
| Journal Title: | Cell Stem Cell |
| Volume: | 4 |
| Issue: | 6 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2009-06-05 |
| Start Page: | 548 |
| End Page: | 558 |
| Language: | English |
| DOI: | 10.1016/j.stem.2009.03.015 |
| PUBMED: | 19497283 |
| PROVIDER: | scopus |
| PMCID: | PMC2914688 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 17" - "Export Date: 30 November 2010" - "Source: Scopus" |
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