Characterization of the First Definitive Hematopoietic Stem Cells in the AGM and Liver of the Mouse Embryo

Abstract

At day 10 in mouse gestation, the intraembryonic aorta-gonads-mesonephros (AGM) region generates the first definitive hematopoietic stem cells (HSCs) of the adult blood system. By 11 days postcoitum, the liver contains such HSCs. While HSCs of the adult bone marrow and late-stage fetal liver have been extensively characterized for cell surface markers, there has been no phenotypic description of the first HSCs during embryo development. We report here the temporal cell surface phenotype of HSCs from the AGM region and early fetal liver and show that all HSCs reside in the c-kit+ population. c-kit+ HSCs from AGM and liver are mainly CD34+ and in the AGM are in both Mac-1+ and Mac-1 fractions. These results demonstrate that during mouse ontogeny the first definitive HSCs are similar in cell surface phenotype to the HSCs of adult bone marrow but that spatial localization and developmental time are critical factors in the phenotypic assessment of this functional cell population.

Yolk-sac hematopoiesis

“…Studies in the mouse embryo have indicated that HSCs able to engraft adult mice are present in the liver beginning at E11-E12 [67][68][69]. These fetal liver-derived HSCs express CD34, c-kit, AA4.1, and Sca-1 surface markers, and are thought to migrate to the bone marrow after E15 [70,71]. Since the liver rudiment is colonized by exogenous blood cells [72], HSCs must arise elsewhere.…”

The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

“…This would allow maximal adaptation to the rapidly changing environments when the developing HSC migrate from the aorta-gonadmesonephros (AGM) to the fetal liver to the BM during embryonic and fetal development. 62,63 HSC might become increasingly epigenetically restricted during development, concurrently with a lessening of the demand for proliferation to fill the growing hematopoietic tissues. There is evidence that the frequency of preleukemic clones is much higher in newborns than the corresponding disease in children.…”

Origins and functions of phagocytes in the embryo

“…Hence, the model of embryonic hematopoiesis (reviewed in [7,8]) in mice suggests the existence of two waves of progenitor cell migration into the liver, one from the yolk sac at 9.5 to 10.0 dpc and the second from the AGM at 10.0 to 10.5 dpc forming a mixed population of progenitors in the liver. Subsequently, only the AGM-derived cells contribute to definite blood cells [9][10][11]. The difference in potential is manifested in the inability of the yolk sac cells to reconstitute an irradiated animal in contrast to those of the fetal liver or bone marrow cells [6,9,[11][12][13].…”

“…Subsequently, only the AGM-derived cells contribute to definite blood cells [9][10][11]. The difference in potential is manifested in the inability of the yolk sac cells to reconstitute an irradiated animal in contrast to those of the fetal liver or bone marrow cells [6,9,[11][12][13].…”