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A perisinusoidal niche for extramedullary haematopoiesis in the spleen

Author

Listed:
  • Christopher N. Inra

    (University of Texas Southwestern Medical Center)

  • Bo O. Zhou

    (University of Texas Southwestern Medical Center)

  • Melih Acar

    (University of Texas Southwestern Medical Center)

  • Malea M. Murphy

    (University of Texas Southwestern Medical Center)

  • James Richardson

    (University of Texas Southwestern Medical Center)

  • Zhiyu Zhao

    (University of Texas Southwestern Medical Center)

  • Sean J. Morrison

    (University of Texas Southwestern Medical Center
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center)

Abstract

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.

Suggested Citation

  • Christopher N. Inra & Bo O. Zhou & Melih Acar & Malea M. Murphy & James Richardson & Zhiyu Zhao & Sean J. Morrison, 2015. "A perisinusoidal niche for extramedullary haematopoiesis in the spleen," Nature, Nature, vol. 527(7579), pages 466-471, November.
    • Handle: RePEc:nat:nature:v:527:y:2015:i:7579:d:10.1038_nature15530
    DOI: 10.1038/nature15530
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    Cited by:

    1. Yu-Jung Tseng & Yuki Kageyama & Rebecca L. Murdaugh & Ayumi Kitano & Jong Hwan Kim & Kevin A. Hoegenauer & Jonathan Tiessen & Mackenzie H. Smith & Hidetaka Uryu & Koichi Takahashi & James F. Martin & , 2024. "Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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