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

Fetal liver hematopoietic stem cell niches associate with portal vessels.

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  • 1Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 2Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
  • 3Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 4Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA.
  • 5Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
  • 6Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 7Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA. paul.frenette@einstein.yu.edu.

Abstract

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.

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PMID:
26634440
PMCID:
PMC4706788
DOI:
10.1126/science.aad0084
[PubMed - indexed for MEDLINE]
Free PMC Article

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