Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 51

hematopoietic stem cell

Notch

common myeloid progenitor double−negative−1cell

granulocyte−macrophage progenitor double−negative−2 cell

double−negative−3 cell

Notch2

Notch3

mast cell thymocyte

Fig. 2.7 Notch pathway in mastocyte development (Source: [ 95 ]). Mastocytes express Notch-1
and Notch-2 morphogens. Hematopoietic stem cells can differentiate into a common myeloid
progenitor that differentiates into a granulocyte-monocyte progenitor. The latter is able to
preferentially generate mastocytes in the presence of Delta-1 that depends on the Notch-2 targets,
HES1 and GATA3 factors. Thymic progenitors that express Notch-1 and Notch-3 and have been
stimulated by Notch, such as DN1 and DN2, can also develop into mastocytes. Factor GATA3 in
thymocytes provokes mastocyte development.

a coordinated manner. Afterward, HES1 overexpression in myeloid progenitors
represses C/EBP α , hence yielding mastocyte development. Downregulation of

C/EBP followed by GATA upregulation due to Notch-2 orchestrates mastocyte

differentiation from myeloid progenitors.
Thymic progenitors that have been stimulated by Notch, such as double-negative
DN1 and DN2 cells, but not those that express preT-cell receptor such as DN3, can
develop into mastocytes. Factor GATA3 engages thymocytes in mastocyte genera-
tion. Commitment to mastocytes and DN3 cells requires Notch downregulation and
maintenance, respectively (Fig. 2.7 ).

α

2.6 Hematopoietic Stem Cells in Angiogenesis

Vasculature repair or hypoxia-primed development is associated by migration
of hematopoietic stem cells from the bone marrow into the blood circulation,
which is initiated by vascular endothelial growth factor and CXCL12 chemokine.
These agents also induce HSC-derived endothelial precursors to participate in
angiogenesis.
Insulin-like growth factor IGF1 binds receptor IGF1R and operates via interac-
tion with IGF-binding proteins (IGFBP1-IGFBP6). The latter serve as transporters
and storage pools for IGF1 in a tissue- and developmental stage-specific man-
ner [ 96 ]. The IGFBP activity is regulated by phosphorylation, polymerization,
association to cell or matrix components, and proteolysis. The IGFBP proteins either