Kinoshita T, Sekiguchi T, Xu M J, Ito Y, Kamiya A, Tsuji K, Nakahata T, Miyajima A
Institute of Molecular and Cellular Bioscience, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7265-70. doi: 10.1073/pnas.96.13.7265.
Embryonic liver is a transient site for definitive hematopoiesis. Along with maturation of the bone marrow and spleen, hematopoietic cells relocate from the liver to their final destinations while the liver starts organizing its own structure and develops numerous metabolic functions toward adult. Recently, it was demonstrated that the signal exerted by oncostatin M (OSM) through gp130 plays a pivotal role in the maturation process of the liver both in vitro and in vivo. However, the molecular basis underlying the termination of embryonic hematopoiesis remains unknown. In this study, we report that primary culture of fetal hepatic cells from embryonic day 14.5 murine embryos supported expansion of blood cells from Lin-Sca-1(+)c-Kit+ cells, giving rise to myeloid, lymphoid, and erythroid lineages. Of interest, promotion of hepatic development by OSM and glucocorticoid strongly suppressed in vitro hematopoiesis. Consistent with these results, hepatic culture from the embryonic day 18.5 liver no longer supported hematopoiesis. These data together with the previous observations suggest that the signals exerted by OSM and glucocorticoid induce hepatic differentiation, which in turn terminate embryonic hematopoiesis and promote relocation of hematopoietic cells.
胚胎肝脏是确定性造血的一个短暂场所。随着骨髓和脾脏的成熟，造血细胞从肝脏迁移到它们的最终目的地，与此同时肝脏开始构建自身结构并发展出许多针对成体的代谢功能。最近有研究表明，抑瘤素M（OSM）通过gp130发挥的信号在肝脏体外和体内的成熟过程中起着关键作用。然而，胚胎造血终止的分子基础仍然未知。在本研究中，我们报告称，来自胚胎第14.5天小鼠胚胎的胎儿肝细胞原代培养支持Lin-Sca-1(+)c-Kit+细胞的血细胞扩增，可产生髓系、淋巴系和红系谱系。有趣的是，OSM和糖皮质激素对肝脏发育的促进作用强烈抑制了体外造血。与这些结果一致，胚胎第18.5天肝脏的肝培养不再支持造血。这些数据与之前的观察结果共同表明，OSM和糖皮质激素发出的信号诱导肝脏分化，进而终止胚胎造血并促进造血细胞的迁移。
