Histometrical and three-dimensional analyses of liver hematopoiesis in the mouse embryo

The development and cytoarchitectures of liver hematopoiesis in the mouse from 10 to 19 days of gestation were examined by light and electron microscopy. In fetal liver hematopoiesis, four stages were identified: Stage I, the onset of hematopoiesis at 10 days; Stage II, expansion of the volume of the hematopoietic compartment at 11 and 12 days; Stage III, the peak in the volume of the hematopoietic compartment at 13 and 14 days; and Stage IV, the involution of hematopoiesis after 15 days. During Stages I-II, hematopoietic stem cells appeared to move from the sinusoidal lumina into primitive hepatic cell cords through the sinusoidal endothelium to give rise to colonies among hepatoblasts. At Stage III, the hematopoietic colonies formed ellipsoidal foci as a structural unit of hematopoiesis. These foci were 35-70 x 20-40 microm in size, and erythroblastic islands could be observed in the center of each. Each island contained central macrophages surrounded by a ring of erythroblasts. The macrophages underwent mitosis, showing close contact with the erythroblasts, after which the hematopoietic foci appeared as cords. At Stage IV, these cord-shaped hematopoietic foci became disrupted, and round solitary foci including macrophages appeared within the hepatic cell cords on meandering sinusoids. In fetal liver hematopoiesis, macrophages could be one of the major cell components comprising the hematopoietic microenvironment, especially at Stages II and III.