@article{f7282d5d9fea42dca35bcc2ce3e03255,
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.",
author = "Khan, {Jalal A.} and Avital Mendelson and Yuya Kunisaki and Alexander Birbrair and Yan Kou and Anna Arnal-Estap{\'e} and Sandra Pinho and Paul Ciero and Fumio Nakahara and Avi Ma'ayan and Aviv Bergman and Miriam Merad and Frenette, {Paul S.}",
note = "Funding Information: We are grateful to the National Institutes of Health (NIH) for support: Integrated Training in Pharmacological Science program (NIGMS T32 063754) and National Heart, Lung, and Blood Institute (NHLBI) Ruth L. Kirschstein National Research Service Award (NRSA) predoctoral M.D./Ph.D. fellowship (F30 943257) to J.A.K.; NHLBI Ruth L. Kirschstein NRSA postdoctoral fellowship F32 HL123224 to A.Me.; R01 grants HL097700, DK056638, and HL069438 to P.S.F.; and R01 grants CA164468 and DA033788 to A.Be. S.P. is a New York Stem Cell Foundation-Druckenmiller Fellow. A.Ma. is supported by U54HL127624, U54CA189201, and R01GM098316. We thank A. L. Kolodkin for providing antibody to Nrp1 and L. Silberstein for RNA-sequencing recommendations. We thank O. Uche and L. Tesfa for technical assistance with sorting and K. O'Connell for technical assistance with Vevo Ultrasound imaging technology. We are also grateful to the New York State Department of Health (NYSTEM Program) for shared facility (C029154) and research support (N13G-262). This work was funded by NIH grants R01 DK056638, R01 HL116340, R01 HL069438, and NYSTEM grants (C029154 and C029570). J.A.K. designed and analyzed experiments in this study. Y.Ku. performed transplantations. J.A.K. and Y.Ku. performed the in vivo experiments. J.A.K., Y.Ku., and A.Me. performed wholemount experiments; J.A.K., A.A.-E., P.C., A.Me, and A.Bi. performed immunostaining. J.A.K. and S.P. performed the LTC-IC experiments; A.Me. and S.P. performed differentiation assays; J.A.K., F.N., and A.Me. performed expression analyses; J.A.K. performed the RNA-sequencing experiments; Y.Ko., A.Ma., and J.A.K. analyzed the RNA-sequencing data; J.A.K. and A.Be. performed computational modeling and statistical analysis of the data; and J.A.K. and P.S.F. wrote the manuscript. The authors declare no competing financial interests.",
year = "2016",
doi = "10.1126/science.aad0084",
language = "English (US)",
volume = "351",
pages = "176--180",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6269",
}
