The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation

Cell Stem Cell. 2008 Mar 6;2(3):252-63. doi: 10.1016/j.stem.2008.01.001.


The mouse placenta was unveiled as an important reservoir for hematopoietic stem cells (HSCs), yet the origin of placental HSCs was unknown. By tracking developing HSCs by expression of Runx1-lacZ and CD41, we have found that HSCs emerge in large vessels in the placenta. Analysis of Ncx1(-/-) embryos, which lack a heartbeat, verified that HSC development is initiated in the placental vasculature independent of blood flow. However, fewer CD41+ hematopoietic cells were found in Ncx1(-/-) placentas than in controls, implying that some HSCs/progenitors colonize the placenta via circulation and/or HSC emergence is compromised without blood flow. Importantly, placentas from Ncx1(-/-) embryos possessed equal potential to generate myelo-erythroid and B and T lymphoid cells upon explant culture, verifying intact multilineage hematopoietic potential, characteristic of developing HSCs. These data suggest that, in addition to providing a niche for a large pool of HSCs prior to liver colonization, the placenta is a true site of HSC generation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage / physiology
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Female
  • Hematopoiesis, Extramedullary / physiology
  • Hematopoietic Stem Cells / physiology*
  • Liver / cytology
  • Liver / embryology*
  • Mice
  • Mice, Knockout
  • Placenta / blood supply*
  • Placenta / cytology
  • Platelet Membrane Glycoprotein IIb / genetics
  • Platelet Membrane Glycoprotein IIb / metabolism
  • Pregnancy / physiology*
  • Sodium-Calcium Exchanger / genetics
  • Sodium-Calcium Exchanger / metabolism


  • Core Binding Factor Alpha 2 Subunit
  • NCX1 protein, mouse
  • Platelet Membrane Glycoprotein IIb
  • Runx1 protein, mouse
  • Sodium-Calcium Exchanger