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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1814-1823.
Prepublished online as a Blood First Edition Paper on May 29, 2007; DOI 10.1182/blood-2007-02-075648.
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HEMATOPOIESIS
The Hedgehog receptor Patched controls lymphoid lineage commitment
Anja Uhmann1,
Kai Dittmann2,
Frauke Nitzki1,
Ralf Dressel2,
Milena Koleva1,
Anke Frommhold1,
Arne Zibat1,
Claudia Binder3,
Ibrahim Adham1,
Mirko Nitsche4,
Tanja Heller5,
Victor Armstrong5,
Walter Schulz-Schaeffer6,
Jürgen Wienands2, and
Heidi Hahn1
1 Institute of Human Genetics,
2 Department of Cellular and Molecular Immunology,
3 Department of Haematology and Oncology,
4 Department of Radiation Therapy and Oncology,
5 Department of Clinical Chemistry, and
6 Department of Neuropathology, Georg August University of Göttingen, Göttingen, Germany
A first step in hematopoiesis is the specification of the lymphoid and myeloid lineages from multipotent progenitor cells in the bone marrow. Using a conditional ablation strategy in adult mice, we show that this differentiation step requires Patched (Ptch), the cell surface–bound receptor for Hedgehog (Hh). In the absence of Ptch, the development of T- and B-lymphoid lineages is blocked at the level of the common lymphoid progenitor in the bone marrow. Consequently, the generation of peripheral T and B cells is abrogated. Cells of the myeloid lineage develop normally in Ptch mutant mice. Finally, adoptive transfer experiments identified the stromal cell compartment as a critical Ptch-dependent inducer of lymphoid versus myeloid lineage commitment. Our data show that Ptch acts as a master switch for proper diversification of hematopoietic stem cells in the adult organism.
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