Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 29

Tabl e 2. 2. Factors of the maintenance of hematopoietic stem cells (Sources: [ 57 , 58 ]; MPL:
myeloproliferative leukemia virus proto-oncogene product). Stromal and parenchymal cells of
the bone marrow (mesenchymal progenitors, osteoblasts, fibroblasts, adipocytes, and reticular and
endothelial cells), endosteal cells (undifferentiated bone-lining cells, bone-forming osteoblasts,
and bone-resorbing osteoclasts), and vascular and perivascular cells of bone marrow sinusoids
secrete factors that promote HSC maintenance. Osteoblasts secrete angiopoietin, thrombopoietin,
and CXC-chemokine ligand-12 (CXCL12). Angiopoietin (also secreted by megakaryocytes and
perivascular cells in the bone marrow) and thrombopoietin (supplied by blood or produced by
stromal cells) promote HSC quiescence; CXCL12 (also secreted by reticular and perivascular
cells) regulates HSC migration (CXCR4: CXC-chemokine receptor-4). Alternative splicing creates
many epican variants (a.k.a. CD44 and homing cell adhesion molecule [HCAM]), especially the
smallest epican S (or hematopoietic CD44h) that is strongly expressed on hematopoietic cells and
long epican L (CD44v). Due to diversity of extracellular domain, epican interacts with numerous
ligands (hyaluronate, fibronectin, collagen-1 and -4, serglycin, osteopontin, etc.).

Factor Receptor, partner

Angiopoietin TIE1/2

Ca 2 + -dependent N-cadherin receptor N-cadherin

Ca 2 + -sensing receptor

Calcium

CXCL12 CXCR4

Osteopontin Epican (CD44), α β 3 -integrin

V

Prostaglandin-E2 Cyclooxygenase and synthase

Sonic Hedgehog Patched

Stem cell factor Stem cell factor receptor (KIT)

Thrombopoietin Thrombopoietin receptor (MPL)

adipocytes secrete neuropillin-1, lipocalin-2, 18 adiponectin, and tumor-necrosis

factor- that can preclude hematopoietic cell proliferation. Although adipocytes

prevent expansion of hematopoietic progenitors, they preserve hematopoietic stem
cell pool.

α

2.3.3 Crosstalk between Niche-Resident Cells

Molecular crosstalk between hematopoietic stem cells and other cellular con-
stituents of endosteal niches regulate the balance between HSC self-renewal and
differentiation. Cellular adhesions between stem cells and stromal cells and/or
the extracellular matrix anchor stem cells within the niche and regulate stem cell
behavior. Whereas

β 7 -integrins are not necessary to maintain retention of
adult hematopoietic precursors in the bone marrow, other agents, such as membrane-

β 1 -and

18 A.k.a. neutrophil gelatinase-associated

lipocalin (NGAL) and migration-stimulating factor

inhibitor (MSFI).