Development of day-8 colony-forming unit-spleen hematopoietic progenitors during early murine embryogenesis: spatial and temporal mapping

Abstract

The ontogeny of the hematopoietic system in mammalian embryos occurs during the yolk sac (YS) and the fetal liver (FL) stages. Events leading to the establishment of hematopoiesis in the FL remain obscure. The appearance of colony-forming units-spleen (CFU-S) in the FL is preceded by a gradual increase of CFU-S in the YS and a more rapid increase in the AGM region (area comprising dorsal aorta, gonads, and mesonephros) during day 10 of development (Medvinsky et al, Nature 364:64, 1993). By this time, the AGM CFU-S attain a high frequency equivalent to that found in the adult bone marrow. The analogous area gives rise to adult hematopoiesis in amphibians and probably in birds. We present here a more complete picture of CFU-S development during transition from the pre-liver to liver stage of hematopoiesis. (1) Dissectional analysis of the mouse AGM region shows the presence of CFU- S both around the dorsal aorta and in the uro-genital ridges. (2) The embryonic gut also shows low but distinctive CFU-S activity. This initial intrabody pattern of CFU-S distribution in murine embryogenesis parallels that found for primordial germ cells. (3) The beginning of definitive liver hematopoiesis is accompanied by wide dissemination of CFU-S in the embryonic tissues. (4) Comparison of spleen colonies arising from the AGM and YS has shown morphologic differences. In contrast to simple erythroid constitution of the YS colonies, a broader variety of cells are found within the AGM-derived colonies that are similar to those derived from 11-day FL. These data suggest a lineage relationship for hematopoietic progenitors between the AGM region and the FL.

The embryonic origins of human haematopoiesis

“…At 7·5 d post‐coitum (DPC), before circulation is established between the embryo and yolk sac, multipotent stem cells capable of lymphoid and myeloid differentiation are found in the P‐Sp region surrounding the dorsal aorta but not in the yolk sac. Furthermore, at 10 DPC this region contains spleen colony‐forming unit (CFU‐S) activity at a frequency greater than yolk sac or liver (Medvinsky et al , 1993, 1996; Dzierzak & Medvinsky, 1995). Together, these findings suggest that HSC within the P‐Sp‐derived AGM at 10 DPC are not derived from circulating yolk sac progenitors, but are generated in situ (Cumano et al , 1996).…”

Embryonic Beginnings of Definitive Hematopoietic Stem Cells

“…Thereafter, CFU-S decrease rapidly in the AGM, with a concomitant increase in CFU-S in the liver. These results demonstrate the presence of potent multilineage progenitors in the AGM region, and their temporal and spatial distribution 16,17 suggest that CFU-S from the AGM region colonize the liver.…”

CFU-S11 activity does not localize solely with the aorta in the aorta-gonad-mesonephros region

“…This was in agreement with the sublocalization of CFU-S 8 that was found at E10. 13 A significant increase in CFU-S 11 was observed between E10 and E12, ie, 4.8-fold for the aorta and 11.2-fold for the UGRs (P Յ .003, as determined by linear regression analysis). At all time points there were more CFU-S 11 in the aorta than in the UGRs (75%, 70%, and 56% of the recovered CFU-S 11 for E10, E11, and E12, respectively).…”