title: Fetal liver hematopoietic stem cell niches associate with portal vessels.
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.
authors.affiliation: Ruth 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.
authors.forename: Jalal A
authors.initials: JA
authors.lastname: Khan
authors.affiliation: Ruth 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.
authors.forename: Avital
authors.initials: A
authors.lastname: Mendelson
authors.affiliation: Ruth 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.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kunisaki
authors.affiliation: Ruth 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.
authors.forename: Alexander
authors.initials: A
authors.lastname: Birbrair
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Kou
authors.affiliation: Ruth 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Arnal-Estapé
authors.affiliation: Ruth 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.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinho
authors.affiliation: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research. Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Ciero
authors.affiliation: Ruth 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.
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakahara
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
authors.affiliation: Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Aviv
authors.initials: A
authors.lastname: Bergman
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: Ruth 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.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
mesh_terms: D000818:Animals; D000941:Antigens / Q000032:analysis; D036388:Ephrin-B2 / Q000032:analysis; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008099:Liver / Q000098:blood supply / Q000196:embryology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D064231:Nestin / Q000032:analysis; D039942:Neuropilin-1 / Q000032:analysis; D021041:Placental Circulation; D011168:Portal System / Q000737:chemistry / Q000196:embryology*; D011247:Pregnancy; D011509:Proteoglycans / Q000032:analysis; D036224:Receptor, EphB4 / Q000032:analysis; D055153:Stem Cell Niche / Q000502:physiology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D036388:Ephrin-B2; D064231:Nestin; D039942:Neuropilin-1; D011509:Proteoglycans; D036224:Receptor, EphB4; D000099216:Chondroitin Sulfate Proteoglycan 4; C000601240:EFNB2 protein, mouse; C577485:Nes protein, mouse; C086681:Ephb4 protein, mouse