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Structural and functional differentiation of sinusoidal endothelial cells
during liver organogenesis in humans
A Couvelard, JY Scoazec, MC Dauge, AF Bringuier, F Potet and G Feldmann
Laboratoire de Biologie Cellulaire and INSERM U327, Faculte de Medicine
Xavier Bichat, Paris, France.
During fetal life, human liver sinusoids, which differentiate between 4 and
12 weeks of gestation from capillaries of the septum transversum, must
support an important hematopoietic function and acquire the structural and
functional characteristics of adult sinusoids. To gain insight into their
differentiation process, we studied the expression of (1) markers of
continuous endothelia, absent from adult sinusoidal endothelial cells
(PECAM-1, CD34, and 1F10); (2) functional markers of adult sinusoidal
endothelial calls (CD4, 1CAM-1, CD32, and CD14); and (3) extracellular
matrix components (laminin, tenascin, fibronectin, and thrombospondin) in
37 fetuses of different gestational ages. We identified two successive
differentiation events. (1) An early structural differentiation, occurring
from 5 to 12 weeks of gestation, was characterized by the loss of
continuous endothelial cell markers and a reduction in the perisinusoidal
amount of laminin and in the deposition of tenascin, fibronectin, and
thrombospondin; at the end of this process, fetal liver sinusoids present
structural characteristics comparable to those of the sinuses in adult
hematopoietic bone marrow. (2) A later functional differentiation was
characterized by the acquisition of the markers of adult sinusoidal
endothelial cells, initiating at 10 weeks of gestation and completed by 20
weeks of gestation; this process likely contributes to adapt liver
sinusoids to the specific functions of the adult hepatic tissue.
Volume 87,
Issue 11,
pp. 4568-4580,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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