Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 24

2.1.2 Hemangioblast

Both hematopoietic and endothelial cells arise from a mesoderm-derived

common precursor, the so-called hemangioblast. 6 Hematopoietic
progenitor cells arise from these bipotential precursors via a subset of early
endothelial cells, i.e., differentiated endothelial cells that have a hematopoietic
potential and form the hemogenic endothelium [ 49 ].
TIE2 high ,SCFR

VEGFR2 +

hemogenic endothelium is transiently generated. Heman-
gioblasts isolated from differentiated mouse embryonic stem cells in culture
generate tightly adherent structures (stage 1) and then non-adherent round cells that
proliferate to generate a mature blast colony (stage 2) [ 50 ]. 7
During

+

)
hematopoietic stem cells emerge directly from the aortic floor into the dorsal aortic
lumen, at least in some species, following egress of Runx1

embryogenesis, SCA1 + ,SCFR + (CD117 + ), CD41 + (Itg α 2B +

endothelial cells from
the aortic ventral wall into the subaortic space [ 51 , 52 ]. Cadherin-5

+

(or vascular
endothelial [VE]-cadherin) endothelial precursors or hemogenic endothelial cells
transiently possess the ability to give rise to multipotent hematopoietic stem
and progenitor cells during vertebrate development ( endothelial-hematopoietic
transition )[ 53 ]. These cells afterward enter the blood circulation to colonize and
differentiate in hematopoietic organs.

+

2.2 Biological Models of Hematopoiesis

Hematopoiesis relies on classical and alternative pathways. Long-term hema-
topoietic stem cells give rise to short-term hematopoietic stem cells that have a
transient ability to self-renew and differentiate into multipotent progenitors [ 54 ].
The latter lack the capacity of self-renewal, but retain multipotency, creating
a series of intermediate progenitors, such as common lymphoid and myeloid
progenitors that further differentiate into lymphoid and granulocyte-macrophage
progenitors, respectively.
Lymphoid-primed multipotent progenitors can develop lymphoid and myeloid
progeny, but not erythroid and megakaryocytic cells.

6 Marker VEGFR2 is also called fetal liver kinase FLK1 and kinase insert domain receptor (KDR).
VEGFR2

+ +

precursors can differentiate into endothelial, primitive and definitive
hematopoietic progenitor cells, cardiomyocytes, and mural cells.
7 At stage 1, a majority of cells is positive for the endothelial marker, angiopoietin-1 TIE2 receptor
(a.k.a. Tyr endothelial kinase [TEK]), whereas a minority of cells is positive for α 2B integrin (or
CD41) that defines hematopoietic engagement. Afterward, the percentage of CD41 + cells rises
and most cells are rapidly CD41 + ,TIE2 − cells. Transient TIE2 high ,SCFR + cell population that
contains both CD41

, cadherin-1

− +

cells hence represents a transitional population from which
definitive hematopoietic progenitors originate.

and CD41