Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 31

Endothelial cells in vascular niche signal to hematopoietic stem and progenitor
cells, as they release specific paracrine growth factors, the so-called angiocrine
factors . Protein kinase-B activation in endothelial cells via TOR, but not the
FoxO pathway, upregulates specific angiocrine factors that support self-renewal
and expansion of CD34

hematopoietic stem
and progenitor cells (LSK cells), hence the long-term hematopoietic stem cell
repopulation [ 929 ]. On the other hand, coactivation in endothelial cells of PKB
and extracellular signal-regulated kinases ERK1 and ERK2 favors maintenance
and lineage-specific differentiation of hematopoietic stem and progenitor cells.
Selective activation of PKB1 in endothelial cells of adult mice increased the
number of colony-forming units in the spleen and CD34

− ,STK1 − ,Lin − ,SCA1 + ,SCFR +

− ,STK1 − , LSK long-term

hematopoietic stem and progenitor cells in the bone marrow [ 929 ].

2.4 Regulation of Hematopoiesis

Hematopoietic stem cells express the plasmalemmal hematopoietic progenitor
antigen cluster of differentiation CD34 (CD34

cells), a glycoprotein (sialomucin
protein) that acts as a cell adhesion molecule for attachment of stem cells to the
extracellular matrix or stromal cells. 21 Expression of CD34 allows activated early
progenitors to be distinguished from quiescent cells. CD34-related molecules —
podocalyxin and podocalyxin-like molecule-2 (or endoglycan) — are also expressed
on stem and early progenitor cells [ 65 , 66 ](Table 2.3 ). 22 Proteins of the CD34
family enhance proliferation, but repress differentiation of stem and progenitor cells,
partly due to defects in adhesion and migration [ 66 ]. Both CD34 and podocalyxin
improve migration of hematopoietic cells. Members of the CD34 family promote or
block cell adhesion according to their expression level. They facilitate adhesion of
lymphocytes to specialized vascular endothelia in lymphoid tissues such as that of
high endothelial venules. On the other hand, their negatively charged, glycosylated
extracellular domain can impede intercellular aggregation [ 66 ].

+

21 CD34 + cells also comprise endothelial progenitor cells, vascular endothelial cells, T lympho-
cytes, mastocytes, and interstitial and dermic dendritic cells, as well as other tissue-specific stem
cells, such as muscle satellite cells and epidermal precursors [ 65 , 66 ].
22 Podocalyxin is also known as podocalyxin-like protein PodxL1 or PCLP1, thrombomucin,
and GP135; and endoglycan as podocalyxin-like protein PodxL2 or PCLP2. Podocalyxin was
originally identified as a marker of kidney glomerular epithelial cells (podocytes). Podocalyxin
is also expressed on vascular endothelial cells and hematopoietic stem and progenitor cells [ 66 ].
Intracellular binding partners of members of the CD34 family include scaffolds sodium-hydrogen
exchanger (NHE) regulatory factors (NHERF1-NHERF2), or solute carrier family SLC8a39
regulators (SLC8a39R1 and -R2), as well as adaptor CRK-like protein (CRKL) [ 66 ]. Both
NHERF1 and NHERF2 possess a C-terminal ezrin-radixin-moesin (ERM)-binding site and 2 PDZ
domains. Although CD34 does not interact with NHERF proteins in hematopoietic progenitor
cells, it operates with CRKL adaptor.