Biology Reference
In-Depth Information
Erythropoiesis: an overview
Lyonel G. Israels
1
and Esther D. Israels
2
1
University of Manitoba and Manitoba Institute of Cell Biology, 675 McDermot Avenue, Winnipeg,
MB Canada R3E 0V9
2
Department of Pediatrics and Child Health, University of Manitoba, 675 McDermot Avenue,
Winnipeg, MB Canada R3E 0V9
Erythrocyte production
Red blood cell production is dynamic and highly regulated. The normal red
cell life-span is approximately 120 days requiring, at equilibrium, a daily
replacement of 0.8% to 1.0% of the circulating red cell pool. Balanced pro-
duction and destruction maintain the red cell mass within relatively narrow
limits. An immediate erythropoietic response is triggered when tissue oxy-
genation is compromised due to blood loss or a shortened red cell life-span, or
when demand increases for oxygen-carrying capacity.
Erythrocytes arise primarily from the CD34
+
pluripotent hematopoietic
stem cells of the bone marrow. These progenitor stem cells constitute approx-
imately 0.1% of the nucleated cells in the bone marrow, only about 5% of
which are in cycle at any one time. The stem cell pool maintains itself,with
little if any depletion, by asymmetric division into a committed colony-form-
ing unit (CFU) and another stem cell. The quiescent stem cell remains in the
G0 or G1 phase of the cell cycle, protected from genotoxic events and with
extended time for DNA repair [1]. Cytokine binding to cell-surface receptors
triggers stem cell activation. The early CFU have a higher proliferative rate but
a more limited self-renewal rate than stem cells. The progeny of pluripotent
CFU are heterogeneous, the result of a stochastic process with the possibility
of more than one cell type evolving from early CFU progenitors; proliferation
and survival are regulated by cytokines [2, 3]. Although most hematopoietic
stem cells reside in the bone marrow, a small number circulate in the periph-
eral blood, as do some of the early CFU cells.
The micro-environment of the bone marrow consists of a network of sinu-
soidal vascular channels with hematopoietic cells, stromal cells, and fat in the
spaces between the venous sinuses. The hematopoietic cells are sequestered in
specific islands and are “nursed” by stromal cells that secrete the cytokines
required for their development. The stromal cells include fibroblasts,
macrophages, dendritic cells, T cells, and osteoblasts. The extracellular matrix
provides a support grid and an adhesive substrate, consisting of collagen,
fibronectin, reticulin, thrombospondin, proteoglycans, and laminin [4, 5]. A
