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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-05-1341.

Submitted May 7, 2002
Accepted December 4, 2002
Fetal liver stroma consists of cells in epithelial-to-mesenchymal transition
Jalila Chagraoui*, Adeline Lepage-Noll, Aurora Anjo, Georges Uzan, and Pierre Charbord
INSERM, Unite 506, Groupe Hospitalier Paul Brousse, Villejuif, France
Laboratoire de Microscopie Electronique du service d'Anatomopathologie, Groupe Hospitalier Paul Brousse, Villejuif, France
Laboratoire d'Hematopoiese, Faculte de Medecine, Tours, France
* Corresponding author; email: jali{at}netcourrier.com.
Liver becomes the predominant site of hematopoiesis by 11.5 day post-coitus in the mouse and 15 gestational weeks in humans, and stays so until the end of gestation. The reason why 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, alpha SM-actin, thrombospondin-1, EDa fibronectin, calponin, Stro-1 antigens, myocyte-enhancer factor 2C) and epithelial (alpha-feto protein, cytokeratin 8 and 18, albumin, E-cadherin, hepatocyte nuclear factor 3alpha) 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 non-hematopoietic 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 HSCs seeding the liver rudiment.

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