Bone marrow adipose tissue-derived stem cell factor mediates metabolic regulation of hematopoiesis

Haematologica. 2019 Sep;104(9):1731-1743. doi: 10.3324/haematol.2018.205856. Epub 2019 Feb 21.


Hematopoiesis is dynamically regulated by metabolic cues in homeostatic and stressed conditions; however, the cellular and molecular mechanisms mediating the metabolic sensing and regulation remain largely obscure. Bone marrow adipose tissue remodels in various metabolic conditions and has been recently proposed as a niche for hematopoietic stem cells after irradiation. Here, we investigated the role of marrow adipose tissue-derived hematopoietic cytokine stem cell factor in unperturbed hematopoiesis by selectively ablating the Kitl gene from adipocytes and bone marrow stroma cells using Adipoq-Cre and Osx1-Cre, respectively. We found that both Adipoq-Kitl knockout (KO) and Osx1-Kitl KO mice diminished hematopoietic stem and progenitor cells and myeloid progenitors in the bone marrow and developed macrocytic anemia at the steady-state. The composition and differentiation of hematopoietic progenitor cells in the bone marrow dynamically responded to metabolic challenges including high fat diet, β3-adrenergic activation, thermoneutrality, and aging. However, such responses, particularly within the myeloid compartment, were largely impaired in Adipoq-Kitl KO mice. Our data demonstrate that marrow adipose tissue provides stem cell factor essentially for hematopoiesis both at the steady state and upon metabolic stresses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adiponectin / metabolism*
  • Adipose Tissue / metabolism*
  • Animals
  • Bone Marrow / metabolism*
  • Bone Marrow Cells / metabolism
  • Cytokines / metabolism
  • Diet, High-Fat
  • Female
  • Hematopoiesis*
  • Male
  • Mice
  • Mice, Knockout
  • Phenotype
  • Receptors, Adrenergic, beta-3 / metabolism
  • Sp7 Transcription Factor / metabolism*
  • Stem Cell Factor / metabolism*
  • Stem Cells / cytology


  • Adiponectin
  • Adipoq protein, mouse
  • Cytokines
  • Receptors, Adrenergic, beta-3
  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • Stem Cell Factor