Histometrical and Three-Dimensional Analyses of Liver Hematopoiesis in the Mouse Embryo.

Abstract

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.

Hematopoietic Microenvironment in the Fetal Liver: Roles of Different Cell Populations

“…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].…”

“…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.…”

Restoration of Liver Mass after Injury Requires Proliferative and Not Embryonic Transcriptional Patterns

“…The first explanation is unlikely, based on the similarity of the 10.5-dpc point, which includes immature red blood cells, the 12.5-dpc point, which includes mature red blood cells, and the 16.5-dpc time point, when hematopoiesis involutes (36,37). Similarly, it is unlikely differences in cell type explain transcriptional differences, as all major cell types present in the mature liver are present in 16.5-dpc livers, including hepatocytes, cholangiocytes, stellate cells, endothelial cells, and macrophage-type cells (38).…”

Interleukin-1 regulates hematopoietic progenitor and stem cells in the midgestation mouse fetal liver

“…The FL also plays a crucial role in erythropoiesis and hematopoietic progenitor cell expansion. [8][9][10] In contrast to the AGM region, which harbors a microenvironment suitable for the generation of HSCs, the FL does not generate HSCs de novo, but is thought to be seeded with HSCs from other embryonic sites (i.e. the AGM and/or the yolk sac).…”