Fetal liver hematopoietic stem cell niches associate with portal vessels

Science. 2016 Jan 8;351(6269):176-80. doi: 10.1126/science.aad0084. Epub 2015 Dec 3.


Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver niche is not yet elucidated. We show that Nestin(+)NG2(+) pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin(+)NG2(+) cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1(+)Ephrin-B2(+) artery to EphB4(+) vein phenotype, associated with a loss of periportal Nestin(+)NG2(+) cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a periportal vascular niche with a fractal-like organization enabled by placental circulation.

Publication types

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

MeSH terms

  • Animals
  • Antigens / analysis
  • Ephrin-B2 / analysis
  • Female
  • Hematopoietic Stem Cells / physiology*
  • Liver / blood supply
  • Liver / embryology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Nestin / analysis
  • Neuropilin-1 / analysis
  • Placental Circulation
  • Portal System / chemistry
  • Portal System / embryology*
  • Pregnancy
  • Proteoglycans / analysis
  • Receptor, EphB4 / analysis
  • Stem Cell Niche / physiology*


  • Antigens
  • EFNB2 protein, mouse
  • Ephrin-B2
  • Nes protein, mouse
  • Nestin
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4
  • Neuropilin-1
  • Ephb4 protein, mouse
  • Receptor, EphB4