During emergency hematopoiesis, HSC differentiate into myeloid-biased multipotent
progenitors (MPP2/ 3) and then into granulocyte-monocyte progenitors (GMPs).
GMPs first organize in loosely collected patches (pGMPs) in the BM and then
condense to form distinct, compact, and transient clusters of GMPs (cGMPs)
tightly surrounded by differentiated myeloid cells (i.e., granulocytes). These
transitions are mediated by stimulatory cytokines, such as IL-1, SCF, and G-CSF,
and inhibited by niche factors, such as TGF-β1 and CXCL4. These factors
are released by megakaryocytes, which restore HSC quiescence and serve as a
negative feedback mechanism for cGMPs. During development of myeloid
malignancies, this mechanism is conserved by a lack of TGF-β1 and CXCL4
and an aberrant β-catenin-Irf8 self-renewal network. MSC, mesenchymal
stromal cell; Meg, megakaryocyte; HSC, hematopoietic stem cell; MPP, multipotent
progenitor; BM, bone marrow.