Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 23

protein NuRR1, or NR4a2, prevents the entry into the cell cycle [ 46 ]. Factor NR4a2
may upregulate cyclin-dependent kinase inhibitor CKI2c.
Connexin-43, a constituent of gap junctions, is synthesized in hematopoietic
stem and progenitor cells. However, it is downregulated during the differentiation
of hematopoietic stem cells to progenitors. Connexin-43 regulates the content of
reactive oxygen species inside stressed hematopoietic stem cells, as it enables ROS
transfer to supporting stromal cells in the hematopoietic environment [ 45 ]. Whereas
low ROS levels are needed for cell activity (Vol. 4 - Chap. 10. Other Major Signaling
Mediators), a sustained increase in ROS production during stress (and aging) can
prevent self-renewal and cause senescence. Hyporegenerative capacity and cell
cycle arrest can result from high levels of ROS and activation of P38MAPK and
FoxO1 agents.
The number of hematopoietic stem cells is assessed to be of the order of
10000 cells. However, the blood cell production rate varies with mammal size. In
addition, the larger the species size, the faster the proliferation rate. The size of the
hematopoietic stem cell pool can be associated with allometric scaling, which is
defined by a simple power law between a given observable y and the mass m of the
organism: 3

y 0 m p

y = . (2.1)

The number of active stem cells in adult mammals evaluated by measuring the
number of circulating reticulocytes scales with body mass with exponent 3/4 [ 47 ].

2.1.1 LSK Hematopoietic Stem Cells

Hematopoietic stem cells belong to a bone marrow cell population that expresses
high levels of stem cell antigen-1 (SCA1) and plasmalemmal stem cell factor recep-
tor (SCFR), 4 but not plasmalemmal markers of lineage-committed hematopoietic

). 5 cells (Lin − This stem cell subset is hence defined as Lin − ,SCA1 + ,SCFR

(KIT) + (LSK) cells.

T cells diversify their activities, unlike antigen-specific T-cell clones, but generally remain
restricted to certain antigens. On the other hand, polyclonal immunoglobulins (antibodies) are
combination of immunoglobulins secreted against a specific antigen, each identifying a different
antigen epitope (antigenic determinant) and generally obtained from different B-cell clones.
3 Allometric scaling can also be applied to basal metabolic rate, heart rate, arterial radii, etc. Most
of the scaling powers

·

p

are multiples of 1/4. Computed power 3/4 can be related to a surface-to-

volume ratio.
4 Membrane-bound stem cell factor, or cellular kinase in tyrosine (KIT or cKIT) ligand, after
proteolytic cleavage, binds and activates SCFR receptor. Membrane-bound stem cell factor
stimulates adhesion of hematopoietic stem and progenitor cells to stromal cells, because it activates
integrins.
5 A lineage marker negative phenotype (Lin

− ) corresponds, in mice, to CD2 − ,CD3 − ,CD4 − ,

CD5 . Hematopoietic stem cells can be precisely

distinguished from other hematopoietic progenitors by the plasmalemmal expression of signaling
lymphocytic activation molecules (SLAM), such as SLAMF1, SLAMF2, and SLAMF4 [ 48 ].

− ,CD8 − , CD161c − ,PTPRc − , Ly76 − , Ly6g −