Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation

Nat Immunol. 2001 Feb;2(2):172-80. doi: 10.1038/84282.


A pool of stem cells that arise from the mesoderm during embryogenesis initiates hematopoiesis. However, factors that regulate the expansion of blood stem cells are poorly understood. We show here that cytokine-induced proliferation of primitive human hematopoietic cells could be inhibited with antibodies to hedgehog (Hh). Conversely, Sonic hedgehog (Shh) treatment induced the expansion of pluripotent human hematopoietic repopulating cells detected in immunodeficient mice. Noggin, a specific inhibitor of bone morphogenetic protein 4 (BMP-4), was capable of inhibiting Shh-induced proliferation in a similar manner to anti-Hh; however, anti-Hh had no effect on BMP-4-induced proliferation. Our study shows that Shh functions as a regulator of primitive hematopoietic cells via mechanisms that are dependent on downstream BMP signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Bone Morphogenetic Proteins / physiology*
  • Carrier Proteins
  • Cell Division / drug effects
  • Cell Division / physiology
  • DNA Primers / genetics
  • Hedgehog Proteins
  • Hematopoiesis / drug effects
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • In Vitro Techniques
  • Models, Biological
  • Proteins / antagonists & inhibitors
  • Proteins / genetics
  • Proteins / pharmacology
  • Proteins / physiology*
  • Trans-Activators*


  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • DNA Primers
  • Hedgehog Proteins
  • Proteins
  • SHH protein, human
  • Trans-Activators
  • noggin protein