Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis

Details

• Alternative Title:
  Cell Stem Cell
• Personal Author:
  Zhao, Jimmy L. ; Ma, Chao ; O'Connell, Ryan M. ; Mehta, Arnav ; DiLoreto, Race ; Heath, James R. ; Baltimore, David
• Description:
  During an infection, the body increases the output of mature immune cells in order to fight off the pathogen. Despite convincing evidence that hematopoietic stem and progenitor cells (HSPCs) can sense pathogens directly, how this contributes to hematopoietic cell output remains unknown. Here, we have combined mouse models with a single-cell proteomics platform to show that, in response to Toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells produce copious amounts of diverse cytokines through nuclear factor κB (NF-κB) signaling. Interestingly, the cytokine production ability of HSPCs trumps mature immune cells in both magnitude and breadth. Among cytokines produced by HSPCs, IL-6 is a particularly important regulator of myeloid differentiation and HSPC proliferation in a paracrine manner and in mediating rapid myeloid cell recovery during neutropenia. This study has uncovered an important property of HSPCs that enables them to convert danger signals into versatile cytokine signals for the regulation of stress hematopoiesis.
• Subjects:
  Animals Article Bone Marrow Cells Cell Differentiation Cells, Cultured Cytokines Female Hematopoiesis Hematopoietic Stem Cells Male Mice Mice, Inbred C57BL Multipotent Stem Cells Myeloid Cells NF-kappa B Signal Transduction Stress, Physiological Toll-Like Receptors

  More +
• Source:
  Cell Stem Cell. 2014; 14(4):445-459.
• Pubmed ID:
  24561084
• Pubmed Central ID:
  PMC4119790
• Document Type:
  Journal Article
• Funding:
  R01CA170689/CA/NCI NIH HHS/United States ; 5U54CA119347/CA/NCI NIH HHS/United States ; T32 GM008042/GM/NIGMS NIH HHS/United States ; DP2 GM111099/GM/NIGMS NIH HHS/United States ; R00 HL102228/HL/NHLBI NIH HHS/United States ; U54 CA119347/CA/NCI NIH HHS/United States ; U54 CA151819/CA/NCI NIH HHS/United States ; F30HL110691/HL/NHLBI NIH HHS/United States ; R01AI079243/AI/NIAID NIH HHS/United States ; R01 CA170689/CA/NCI NIH HHS/United States ; R01 AI079243/AI/NIAID NIH HHS/United States ; DP2GM111099/DP/NCCDPHP CDC HHS/United States ; F30 HL110691/HL/NHLBI NIH HHS/United States ; R00HL102228/HL/NHLBI NIH HHS/United States
• Volume:
  14
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:0163b3bcaeeff56c3577a6aed05c2b2f3afe32de6cdf80aee3d950e8d1756e39
• Download URL:
  https://stacks.cdc.gov/view/cdc/30060/cdc_30060_DS1.pdf
• File Type:
  [PDF - 2.98 MB ]