Biomedical Engineering Reference
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(
15% of cellular H2A) involved in double-stranded break repair [
94
]. Primary
human, short-lived, blood cells, in which H2AX level is substantially reduced by
miR24 overexpression, then become vulnerable to DNA damage.
50
∼
2.4.4
Other Regulators
2.4.4.1
Cyclooxygenases and Prostaglandins
Cyclooxygenases Cox1 and Cox2, PGE2-synthase, and prostaglandin-E2 are in-
volved in hematopoiesis [
58
]. Prostaglandin-E2 augments the number of hematopoi-
etic stem cells. Cyclooxygenase-1 serves in the formation of the hematopoietic
niche, whereas Cox2 probably intervenes in HSC self-renewal and proliferation.
Inhibitors of COx1 or COx2 diminish CFU activity.
2.4.4.2
Calcium-Sensing Receptor
Hematopoietic stem cells without the calcium-sensing receptor (Vol. 3 - Chap. 7. G-
Protein-Coupled Receptors) can engraft in extramedullary spaces, such as the spleen
or liver, and produce extramedullary hematopoiesis.
2.5
Mastocyte Formation
Mastocytes regulate physiologic and pathologic immune response, as they protect
against parasites and bacteria and mediate allergy and autoimmunity.
Stem cell factor and IL3, via the PI3K, Ras-MAPK, and JaK-STAT pathways
influence mastocyte number and type. Upregulation of SPI1 and GATA2 factors
and downregulation of CCAAT/enhancer-binding protein-
α
cooperate to generate
mastocytes.
Mastocytes leave the bone marrow as mastocyte progenitors that mature in
target tissues. Notch signaling connects environmental cues and transcriptional
control that increases mastocyte development [
95
]. Notch ligand Delta-1 instructs
common myeloid progenitors and granulocyte-macrophage progenitors in the bone
marrow toward mastocyte lineage at the expense of other granulocyte-macrophage
lineages due to Notch-2. Notch-2 upregulates GATA3 (not GATA2 although
GATA2 is required for in vitro mastocyte generation) and HES1 expression in
50
During double-stranded break repair, H2AX is phosphorylated by phosphatidylinositol 3-kinase.
Phosphorylated H2AX then participates in DNA repair, replication, recombination and regulation
of the cell cycle, as it binds various cell cycle and DNA-repair factors.
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