Lymphatic vessels arise from specialized angioblasts within a venous niche

J. Nicenboim, G. Malkinson, T. Lupo, L. Asaf, Y. Sela, O. Mayseless, L. Gibbs-Bar, N. Senderovich, T. Hashimshony, M. Shin, A. Jerafi-Vider, I. Avraham-Davidi, V. Krupalnik, R. Hofi, G. Almog, J. W. Astin, O. Golani, S. Ben-Dor, P. S. Crosier, W. Herzog, N. D. Lawson, J. H. Hanna, I. Yanai and K. Yaniv ()
Additional contact information
J. Nicenboim: Weizmann Institute of Science
G. Malkinson: Weizmann Institute of Science
T. Lupo: Weizmann Institute of Science
L. Asaf: Weizmann Institute of Science
Y. Sela: Weizmann Institute of Science
O. Mayseless: Weizmann Institute of Science
L. Gibbs-Bar: Weizmann Institute of Science
N. Senderovich: Faculty of Biology, Technion – Israel Institute of Technology
T. Hashimshony: Faculty of Biology, Technion – Israel Institute of Technology
M. Shin: Cell, and Cancer Biology, University of Massachusetts Medical School
A. Jerafi-Vider: Weizmann Institute of Science
I. Avraham-Davidi: Weizmann Institute of Science
V. Krupalnik: Weizmann Institute of Science
R. Hofi: Weizmann Institute of Science
G. Almog: Weizmann Institute of Science
J. W. Astin: School of Medical Sciences, University of Auckland
O. Golani: Biological Services Unit, Weizmann Institute of Science
S. Ben-Dor: Biological Services Unit, Weizmann Institute of Science
P. S. Crosier: School of Medical Sciences, University of Auckland
W. Herzog: University of Muenster
N. D. Lawson: Cell, and Cancer Biology, University of Massachusetts Medical School
J. H. Hanna: Weizmann Institute of Science
I. Yanai: Faculty of Biology, Technion – Israel Institute of Technology
K. Yaniv: Weizmann Institute of Science

Nature, 2015, vol. 522, issue 7554, 56-61

Abstract: Abstract How cells acquire their fate is a fundamental question in developmental and regenerative biology. Multipotent progenitors undergo cell-fate restriction in response to cues from the microenvironment, the nature of which is poorly understood. In the case of the lymphatic system, venous cells from the cardinal vein are thought to generate lymphatic vessels through trans-differentiation. Here we show that in zebrafish, lymphatic progenitors arise from a previously uncharacterized niche of specialized angioblasts within the cardinal vein, which also generates arterial and venous fates. We further identify Wnt5b as a novel lymphatic inductive signal and show that it also promotes the ‘angioblast-to-lymphatic’ transition in human embryonic stem cells, suggesting that this process is evolutionarily conserved. Our results uncover a novel mechanism of lymphatic specification, and provide the first characterization of the lymphatic inductive niche. More broadly, our findings highlight the cardinal vein as a heterogeneous structure, analogous to the haematopoietic niche in the aortic floor.

Date: 2015
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DOI: 10.1038/nature14425

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