Hematopoietic Stem Cells in the Mouse Embryonic Yolk Sac

Abstract

Abstract. The yolk sac is the first site of hematopoiesis during mammalian development. The yolk sac is also the first site of blood vessel development. Development of the blood islands in the yolk sac is an integrated process in which these two developmental events, hematopoiesis and vasculogenesis, proceed in concert. This review focuses on mouse yolk sac hematopoietic stem cells (YS-HSC), describing their differentiation in vitro and in vivo. YS-HSC go through a progressive series of changes prior to the initiation of lineage-specific differentiation. Experiments tracing their origins from postulated hemangioblasts, and the subsequent interaction between these stem cells and yolk sac endothelial cells are described. Differences between the extraembryonic YS-HSC and HSC found later within the embryo, perinatally or in adults, are described. YS-HSC have greater reproductive capability than HSC obtained from fetal liver, umbilical cord blood or adult bone marrow; they do not yet express major histocompatibility complex-associated antigens and they are able to reconstitute adult immunocompromised animals even when introduced in small numbers (<100 cells/mouse). With recent results demonstrating the feasibility of expanding YS-HSC in vitro as well as of introducing new genes into these cells by transfection, the YS-HSC shows promise both as a means of achieving long-term restitution of hematopoiesis across histocompatibility barriers and as a self-renewing vehicle for gene transfer.

Functional endothelial cells derived from rhesus monkey embryonic stem cells

“…11,58 Several studies using mouse ES cells identify an Flk-1 ϩ hemangioblast cell that serves as a common precursor for both blood and endothelial cells. 3,4 Other studies using dissection of timed mouse embryos suggest that common hematopoietic and endothelial cell precursors arise within the developing yolk sac and aorta-gonad-mesonephric region.…”

“…3,4 Other studies using dissection of timed mouse embryos suggest that common hematopoietic and endothelial cell precursors arise within the developing yolk sac and aorta-gonad-mesonephric region. 54,[58][59][60] Specific transcription factors such as SCL and Runx1 required for hemangioblast development have been identified and absence of these genes prevents normal development of both lineages. 5,61 Similar characterization of human (or nonhuman primate) ES cell-derived hemangioblasts has not yet been done.…”

The role of Homeobox genes in normal hematopoiesis and hematological malignancies

“…The anatomical site of hematopoiesis changes during early life phases (reviewed by Zon 10 and Auerbach 11 ). During embryogenesis, early hematopoiesis occurs in the yolk sac, starting in humans at day 15 and continuing for 6 weeks.…”

Developmental Platelet Endothelial Cell Adhesion Molecule Expression Suggests Multiple Roles for a Vascular Adhesion Molecule

“…16,17 Murine embryonic stem (ES) cells are derived from the inner cell mass of blastocysts and are totipotent. ES cells differentiated in culture undergo a programed differentiation that recapitulates normal developmental events in the yolk sac, including vascular and hematopoietic development.…”