The hedgehog receptor Patched1 regulates myeloid and lymphoid progenitors by distinct cell-extrinsic mechanisms

Siggins, S. L., Nguyen, N. Y. N., McCormack, M. P., Vasudevan, S, Villani, R, Jane, S. M., Wainwright, B. J. and Curtis, D. J. (2009) The hedgehog receptor Patched1 regulates myeloid and lymphoid progenitors by distinct cell-extrinsic mechanisms. BLOOD, 114 5: 995-1004. doi:10.1182/blood-2009-03-208330


Author Siggins, S. L.
Nguyen, N. Y. N.
McCormack, M. P.
Vasudevan, S
Villani, R
Jane, S. M.
Wainwright, B. J.
Curtis, D. J.
Title The hedgehog receptor Patched1 regulates myeloid and lymphoid progenitors by distinct cell-extrinsic mechanisms
Journal name BLOOD   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2009-07
Year available 2009
Sub-type Article (original research)
DOI 10.1182/blood-2009-03-208330
Volume 114
Issue 5
Start page 995
End page 1004
Total pages 10
Editor Dr. Sanford J. Shattil
Place of publication Washington , D.C., U.S.A.
Publisher American Society of Hematology
Collection year 2010
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
060406 Genetic Immunology
Abstract Hedgehog (Hh) ligands bind to the Patched1 (Ptch1) receptor, relieving repression of Smoothened, which leads to activation of the Hh signaling pathway. Using conditional Ptch1 knockout mice, the aim of this study was to determine the effects of activating the Hh signaling pathway in hematopoiesis. Surprisingly, hematopoietic-specific deletion of Ptch1 did not lead to activation of the Hh signaling pathway and, consequently, had no phenotypic effect. In contrast, deletion of Ptch1 in nonhematopoietic cells produced 2 distinct hematopoietic phenotypes. First, activation of Hh signaling in epithelial cells led to apoptosis of lymphoid progenitors associated with markedly elevated levels of circulating thymic stromal lymphopoietin. Second, activation of Hh signaling in the bone marrow cell niche led to increased numbers of lineage-negative c-kit+ Sca-1+ bone marrow cells and mobilization of myeloid progenitors associated with a marked loss of osteoblasts. Thus, deletion of Ptch1 leads to hematopoietic effects by distinct cell-extrinsic mechanisms rather than by direct activation of the Hh signaling pathway in hematopoietic cells. These findings have important implications for therapeutics designed to activate the Hh signaling pathway in hematopoietic cells including hematopoietic stem cells.
Keyword HEMATOPOIETIC STEM-CELLS
MICE
NICHE
DIFFERENTIATION
OSTEOBLASTS
MEDULLOBLASTOMA
MOBILIZATION
COMMITMENT
PRECURSORS
PARADIGMS
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 04 Sep 2009, 10:25:23 EST