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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-05-1341.
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Blood, 15 April 2003, Vol. 101, No. 8, pp. 2973-2982
HEMATOPOIESIS
Fetal liver stroma consists of cells in epithelial-to-mesenchymal
transition
Jalila Chagraoui,
Adeline Lepage-Noll,
Aurora Anjo,
Georges Uzan, and
Pierre Charbord
From INSERM U506, Hôpital Paul Brousse,
Villejuif, France; Laboratoire de Microscopie Electronique du service
d'Anatomopathologie, Hôpital Paul Brousse, Villejuif,
France; and Laboratoire
d'Hématopoïèse, Faculté de Médecine,
Tours, France.
Liver becomes the predominant site of hematopoiesis by 11.5 dpc
(days after coitus) in the mouse and 15 gestational weeks in
humans and stays so until the end of gestation. The reason the liver is
the major hematopoietic site during fetal life is not clear. In this
work, we tried to define which of the fetal liver microenvironmental
cell populations would be associated with the development of
hematopoiesis and found that a population of cells with mixed
endodermal and mesodermal features corresponded to
hematopoietic-supportive fetal liver stroma. Stromal cells generated
from primary cultures or stromal lines from mouse or human fetal liver
in the hematopoietic florid phase expressed both mesenchymal markers
(vimentin, osteopontin, collagen I,  smooth muscle actin,
thrombospondin-1, EDa fibronectin, calponin, Stro-1 antigens,
myocyte-enhancer factor 2C) and epithelial (-fetoprotein, cytokeratins 8 and 18, albumin, E-cadherin, hepatocyte nuclear factor 3 ) markers. Such a cell population fits with the description of cells
in epithelial-to-mesenchymal transition (EMT), often observed during
development, including that of the liver. The hematopoietic supportive
capacity of EMT cells was lost after hepatocytic maturation, induced by
oncostatin M in the cell line AFT024. EMT cells were observed in the
fetal liver microenvironment during the hematopoietic phase but not in
nonhematopoietic liver by the end of gestation and in the adult. EMT
cells represent a novel stromal cell type that may be generated from
hepatic endodermal or mesenchymal stem cells or even from circulating
hematopoietic stem cells (HSCs) seeding the liver rudiment.
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