5 FL hepatoepithelial-enriched cell preparations (c-KitDCD45−Ter119−), the remaining CD49fD cells neither differentiated nor survived in vitro. Indeed, direct cell-to-cell contact between the CD49fHCD41H and CD49fD populations was required to promote the hepatocyte differentiation of CD49fD cells. The addition of vascular endothelial growth factor A (VEGF-A) and medium conditioned by E11.5 CD49fHCD41H MKPs STA-9090 produced a partial effect on CD49fD cells, inducing the formation of hepatoepithelial layers. This effect was abolished by anti-VEGF-A antibodies. Together, these findings strongly suggest that CD49fHCD41H MKPs are fundamental

to promote FL development, as proposed in adult liver regeneration. Conclusion: The cells of the MK lineage present in the developing mouse embryo liver promote the growth of hepatoepithelial cells in vitro through VEGF-A signaling and may http://www.selleckchem.com/products/pf-562271.html play a role in liver development in vivo. (HEPATOLOGY 2012;56:1934–1945) After gastrulation, genetic prepatterns are established in discrete areas of the embryo related to cell-lineage specification, cell differentiation, and morphogenesis. Hematopoiesis occurs in two phases in the embryo (primitive and definitive). Primitive hematopoiesis involves embryonic erythrocytes and myeloid cells, commencing in the yolk sac

(YS) and proceeding as a self-limiting process throughout gestation. By contrast, definitive lymphohematopoiesis begins in the YS and, in an autonomous manner, in the para-aortic splanchnopleura/aorta-gonads-mesonephros (P-Sp/AGM) niche, which later becomes the source of all lymphoid and hematopoietic cell lineages.1-3 Megakaryocytes (MKs)

are a particular blood cell type that share common features with hematopoietic stem cells (HSCs). In the adult, CD45+CD9+ CD41++ MKs are found primarily in the bone marrow (BM) as a scattered polyploid population of large cells. These MKs are responsible for the production of platelets, subcellular fragments involved in coagulation and the regulation of angiogenesis.4 In the mouse embryo, clonogenic bipotential megakaryocyte/erythroid 上海皓元 progenitors (MEPs) appear in the YS at embryonic days 7.25 (E7.25) and E9.5, participating in primitive and definitive megakaryopoiesis, respectively.5, 6 At E10.5, large, immature reticulated platelets have been found in the bloodstream, and CD45−CD41H cells can be observed in vascular hematopoietic clusters.5, 7 With the discovery of thrombopoietin (TPO), MKs could be cultured, and platelets were generated in vitro from mature MKs, isolated by density purification, that produce long, pseudopodial cytoplasmic processes (i.e., proplatelets).8 After E10.