The Ikaros family and the development of early intraembryonic hematopoietic stem cells.

Abstract

It is currently well established that across evolutionarily distant species the first blood-forming stem cells appear in the blood islands of both the extraembryonic yolk sac and the embryo proper. Following this initial and only transient generation of primitive erythroid-lineage cells, the major hematopoietic regions are thereafter located in the intraembryonic mesenchyme of the early embryos. Taking advantage of avian yolk sac-embryo chimeras it was originally shown that lymphoid cells are of intraembryonic origin [1, 2]. Two decades after the avian grafting experiments, the murine para-aortic splanchnopleura (P-Sp) and the aorta-gonad-mesonephrosregion (AGM) were functionally characterized to have lymphoid potential [3, 4]. These results confirmed the intraembryonic sources for murine lymphopoiesis. Thus, mesodermal foci, i.e. the splanchnopleura and the ventrally derived intraaortic clusters as well as the later appearing dorsal mesentery-derived para-aortic loci, initiate development of hematopoietic stem cells (HSCs). Although the AGM region is already known to harbor committed progenitors, and lymphoid potential has been shown to reside even in the para-aortic splanchnopleura, the exact time schedule of fate decisions is still rather controversial and unresolved. Contradictory evidence exists concerning the role of the P-Sp/AGM area on one hand as a de novo generator of intraembryonic hematopoietic stem cells and on the other hand as a site of hematopoietic differentiation. It has been postulated that these early hematopoietic environments only give rise to hematopoietic stem cells and further differentiation occurs in the lymphoid organs after colonization [5]. By contrast however, there are data showing the presence of committed lymphocyte progenitors not only in the fetal liver, but also in the murine AGM [6]. These results that are based on a clonal assay system support the idea of early lineage-determination in the lymphoid system. Taken together, these findings confirm not only the intraembryonic origin of the lymphoid cells, but also support the idea of early fate determination occurring before seeding of the primordial lymphoid organs.KeywordsHematopoietic Stem CellLymphocyte DevelopmentStern CellIkaros FamilyIkaros ProteinThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.