Hematopoiesis - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 46

SC

GM−CSF

TGF β

−

CFU−GEMM

SCF

Epo

BFU−Meg

IL

CFU−Meg

MegCSF

megakaryoblast

Tpo

promegakaryocyte

megakaryocyte

platelet−forming megakaryocyte reserve megakaryocyte

thrombocyte

Fig. 2.5 Platelet formation in the bone marrow (SC: stem cell; CFUmeg: colony-forming
unit-megakaryocyte). Many growth factors participate in the genesis of thrombocytes, such as
thrombopoietin (Tpo), erythropoietin (Epo), as well as granulocyte-monocyte (gmCSF or CSF2)
and megakaryocyte (megCSF) colony stimulating factor, in addition to stem cell factor (SCF).
Early-acting megCSF and late-acting Tpo and other megakaryocyte potentiators stimulate mat-
uration of megakaryocytes. Ligands that specifically binds to TpoR receptor on megakaryocytes
have a potent thrombocytopoietic effect. Among interleukins, IL1, IL3, IL5 to IL7, IL9, IL11, and
IL12 are implicated in different stages of thrombopoiesis. Transforming growth factor- )

inhibits the formation of colony-forming unit granulocyte-erythroid-macrophage-megakaryocyte
(CFUgemm) and burst-forming unit megakaryocyte (BFUmeg).

β (TGF β

Granulocyte colony-stimulating factor receptor (gCSFR) is synthesized by
hematopoietic progenitors and mature hematopoietic cells, as well as bone marrow
stromal cells. It targets signal transducer and activator of transcription STAT5 47
and ERK to support proliferation, survival and differentiation of neutrophilic
progenitors. Suppressor of cytokine signaling proteins (SOCS) inhibits gCSFR

47 Different STAT5 isoforms are activated during the early and late differentiation stages of
granulocytes. The transcription factors Signal transducers and activators of transcription (STAT)
reside in a latent form in the cytoplasm and become phosphorylated by Janus kinases (JaK).
Receptor gCSFR activates neither JaK1, JaK2, TyK2, STAT1, nor STAT3 in neutrophils upon gCSF
stimulation [ 87 ].