The Hedgehog receptor Patched controls lymphoid lineage commitment

Blood. 2007 Sep 15;110(6):1814-23. doi: 10.1182/blood-2007-02-075648. Epub 2007 May 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation
  • Cell Lineage*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Female
  • Flow Cytometry
  • Granulocytes / cytology
  • Granulocytes / metabolism
  • Hematopoiesis
  • Immunophenotyping
  • Integrases / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Myeloid Cells / cytology
  • Myeloid Cells / metabolism
  • Patched Receptors
  • Patched-1 Receptor
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Stem Cells / cytology
  • Stromal Cells / cytology
  • Stromal Cells / metabolism
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Thymus Gland / pathology
  • Time Factors

Substances

  • DNA-Binding Proteins
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Ptch1 protein, mouse
  • Rag2 protein, mouse
  • Receptors, Cell Surface
  • Cre recombinase
  • Integrases