Figure 1.
Figure 1. Inflammatory signals regulate HSC fate. (A) Adult hematopoiesis. Under homeostatic conditions, hematopoietic output is dominated by lineage-biased MPP subsets, particularly the numerically most abundant MPP4 compartment, which generates primarily myeloid and lymphoid output, resulting in balanced blood production. On the other hand, the megakaryocyte/erythroid (Meg/E)-biased MPP2 and myeloid-biased MPP3 are less numerous and may contribute little to normal homeostasis. The phenotypic HSC compartment also includes a subset of metabolically active HSCs, termed MPP1, which likely serves as a “ready” compartment for rapid activation during acute need. Under homeostatic conditions, this system is regulated by BM niche signals and basal levels of proinflammatory cytokines, which maintains a balance between HSC dormancy and lineage priming. In response to proinflammatory signals or during hematopoietic regeneration, the HSC compartment undergoes distinct fate changes, including transient proliferation, expansion of MPP1, and the activation of instructive lineage-specific programs in subsets of HSCs. These include Meg priming in CD41+ cells following IFN, TNF, and IL-1 exposure, as well as activation of C/EBPβ and PU.1 in response to IFN-γ and IL-1, respectively. These lineage-primed HSCs in turn lead to expansion of Meg/E-biased MPP2 and myeloid-biased MPP3, likely resulting in rapid production of platelets and myeloid populations. Meanwhile, lymphoid output is suppressed via inflammatory reprogramming of MPP4, resulting in additional myeloid production. (B) Embryonic development. Proinflammatory factors produced in the AGM by myeloid cells from the primitive hematopoietic wave, as well as from other sources, directly activate NF-κB and STAT3 in hemogenic endothelial cells, leading to increased expression of Notch ligands, hence promoting HSC specification. Thus, inflammatory signals have emerged as central players in controlling developmental pathways required for HSC emergence. These findings suggest a close evolutionary and functional relationship between inflammation and tissue development. G-CSF, granulocyte colony-stimulating factor.

Inflammatory signals regulate HSC fate. (A) Adult hematopoiesis. Under homeostatic conditions, hematopoietic output is dominated by lineage-biased MPP subsets, particularly the numerically most abundant MPP4 compartment, which generates primarily myeloid and lymphoid output, resulting in balanced blood production. On the other hand, the megakaryocyte/erythroid (Meg/E)-biased MPP2 and myeloid-biased MPP3 are less numerous and may contribute little to normal homeostasis. The phenotypic HSC compartment also includes a subset of metabolically active HSCs, termed MPP1, which likely serves as a “ready” compartment for rapid activation during acute need. Under homeostatic conditions, this system is regulated by BM niche signals and basal levels of proinflammatory cytokines, which maintains a balance between HSC dormancy and lineage priming. In response to proinflammatory signals or during hematopoietic regeneration, the HSC compartment undergoes distinct fate changes, including transient proliferation, expansion of MPP1, and the activation of instructive lineage-specific programs in subsets of HSCs. These include Meg priming in CD41+ cells following IFN, TNF, and IL-1 exposure, as well as activation of C/EBPβ and PU.1 in response to IFN-γ and IL-1, respectively. These lineage-primed HSCs in turn lead to expansion of Meg/E-biased MPP2 and myeloid-biased MPP3, likely resulting in rapid production of platelets and myeloid populations. Meanwhile, lymphoid output is suppressed via inflammatory reprogramming of MPP4, resulting in additional myeloid production. (B) Embryonic development. Proinflammatory factors produced in the AGM by myeloid cells from the primitive hematopoietic wave, as well as from other sources, directly activate NF-κB and STAT3 in hemogenic endothelial cells, leading to increased expression of Notch ligands, hence promoting HSC specification. Thus, inflammatory signals have emerged as central players in controlling developmental pathways required for HSC emergence. These findings suggest a close evolutionary and functional relationship between inflammation and tissue development. G-CSF, granulocyte colony-stimulating factor.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal