ZFIN ID: ZDB-PUB-141230-19
Inflammatory signaling regulates hematopoietic stem and progenitor cell emergence in vertebrates
He, Q., Zhang, C., Wang, L., Zhang, P., Ma, D., Lv, J., Liu, F.
Date: 2015
Source: Blood   125(7): 1098-106 (Journal)
Registered Authors: Liu, Feng, Ma, Dongyuan, Wang, Lu, Zhang, Chunxia, Zhang, Panpan
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/drug effects
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Hematopoiesis/drug effects
  • Hematopoiesis/physiology*
  • Hematopoietic Stem Cells/drug effects*
  • Hematopoietic Stem Cells/physiology*
  • Inflammation/metabolism
  • Inflammation Mediators/pharmacology
  • Inflammation Mediators/physiology*
  • Male
  • Mice
  • NF-kappa B/metabolism
  • Signal Transduction/immunology
  • Toll-Like Receptor 4/metabolism
  • Zebrafish
PubMed: 25540193 Full text @ Blood
Inflammatory signaling has been shown essential for stress hematopoiesis in adult bone marrow, either through increasing proliferation or by directing differentiation of hematopoietic stem and progenitor cells (HSPCs) towards myeloid or lymphoid lineages. However, its role in embryonic normal hematopoiesis has been unknown. Here, we demonstrate that in both zebrafish and mouse embryos, inflammatory signaling is necessary and sufficient for HSPC emergence, in the absence of infection or pathological inflammation. Mechanistically, inflammatory signaling regulates hemogenic endothelium-derived HSPC development through a conserved TLR-NFκB core signaling, which then promotes Notch activity, a well-known signal required for HSPC specification in vertebrates. Our findings establish a previously unrecognized link between inflammatory signaling and HSPC emergence, and provide new insights into regenerative medicine and novel therapies to treat innate immune-related diseases.