A perisinusoidal niche for extramedullary haematopoiesis in the spleen

Nature. 2015 Nov 26;527(7579):466-471. doi: 10.1038/nature15530. Epub 2015 Nov 16.


Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here we assessed the sources of the key niche factors, SCF (also known as KITL) and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21(+) stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21(+) stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21(+) stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells, or of Scf or Cxcl12 from Tcf21+ stromal cells, severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21(+) stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Blood Cell Count
  • Chemokine CXCL12 / deficiency
  • Chemokine CXCL12 / metabolism
  • Endothelial Cells / metabolism
  • Erythropoiesis
  • Female
  • Hematopoiesis, Extramedullary*
  • Hematopoietic Stem Cells / cytology*
  • Hemorrhage / physiopathology
  • Male
  • Mice
  • Pregnancy
  • Spleen / blood supply
  • Spleen / cytology*
  • Spleen / metabolism
  • Stem Cell Factor / deficiency
  • Stem Cell Factor / metabolism
  • Stem Cell Niche*
  • Stromal Cells / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Stem Cell Factor
  • Tcf21 protein, mouse

Associated data

  • GEO/GSE71288