Hematopoiesis is the main function of the liver during a considerable period of mammalian prenatal development. Hematopoietic cells of the fetal liver exist in a specific microenvironment that controls their proliferation and differentiation. This microenvironment is created by different cell populations, including epitheliocytes, macrophages, various stromal elements (hepatic stellate cells, fibroblasts, myofibroblasts, vascular smooth muscle and endothelial cells, mesenchymal stromal cells), and also cells undergoing epithelial-to-mesenchymal transition. This paper considers the involvement of these cell types in the regulation of fetal liver hematopoiesis. 1. Introduction In mammals, the liver serves as the main hematopoietic organ during a considerable period of prenatal ontogeny. In murine liver, for example, hematopoietic cells first appear in 10-day embryos, with hematopoietic function of the organ reaching a peak on embryonic days 13–14 and ceasing during the first 2–4 postnatal days [1, 2]. Hematopoiesis requires specific microenvironment that produces chemical signals to attract hematopoietic cells and regulates their proliferation and differentiation via contact and humoral interactions. The hematopoietic microenvironment of the fetal liver is created by a complex of cell types, including epitheliocytes, resident macrophages, and several stromal cell populations of mesenchymal origin such as hepatic stellate cells, fibroblasts, myofibroblasts, vascular smooth muscle and endothelial cells, and mesenchymal stromal cells (MSCs). Let us consider the roles of different cell components of this microenvironment in the maintenance of hematopoietic activity in the developing liver. 2. Liver Epithelium At early stages of liver development, its epithelium is represented by bipotent hepatoblasts, which subsequently differentiate into hepatocytes and cholangiocytes [1, 2]. Hepatoblasts can be identified by the simultaneous expression of both hepatic (cytokeratin 18, albumin) and biliary epithelial markers (cytokeratin 19) and also of E-cadherin [3]. The morphology and phenotype of liver epithelial cells change in the course of development, and these changes correlate with hematopoietic activity [4, 5]. Cells of the hepatocyte lineage appear to play an important role in the regulation of erythropoiesis: they closely interact with erythroblasts [5] and produce erythropoietic cytokines such as stem cell factor and erythropoietin [6, 7]. Localization of megakaryocyte lineage cells among hepatocytes described in human fetal liver [8] and thrombopoietin
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