Bone marrow remodeling supports hematopoiesis in response to immune thrombocytopenia progression in mice

Oliver J Herd, Gulab Fatima Rani, James P Hewitson, Karen Hogg, Andrew P Stone, Nichola Cooper, David G Kent, Paul G Genever, Ian S Hitchcock

Research output: Contribution to journalArticlepeer-review


Immune thrombocytopenia (ITP) is an acquired autoimmune condition characterized by both reduced platelet production and the destruction of functionally normal platelets by sustained attack from the immune system. However, the effect of prolonged ITP on the more immature hematopoietic progenitors remains an open area of investigation. By using a murine in vivo model of extended ITP, we revealed that ITP progression drives considerable progenitor expansion and bone marrow (BM) remodeling. Single-cell assays using Lin-Sca1+c-Kit+CD48-CD150+ long-term hematopoietic stem cells (LT-HSCs) revealed elevated LT-HSC activation and proliferation in vitro. However, the increased activation did not come at the expense of LT-HSC functionality as measured by in vivo serial transplantations. ITP progression was associated with considerable BM vasodilation and angiogenesis, as well as a twofold increase in the local production of CXCL12, a cytokine essential for LT-HSC function and BM homing expressed at high levels by LepR+ BM stromal cells. This was associated with a 1.5-fold increase in LepR+ BM stromal cells and a 5.5-fold improvement in progenitor homing to the BM. The increase in stromal cells was transient and reverted back to baseline after platelet count returned to normal, but the vasculature changes in the BM persisted. Together, our data demonstrate that LT-HSCs expand in response to ITP and that LT-HSC functionality during sustained hematopoietic stress is maintained through an adapting BM microenvironment.

Original languageEnglish
Pages (from-to)4877-4889
Number of pages13
JournalBlood Advances
Issue number23
Early online date24 Aug 2021
Publication statusPublished - 14 Dec 2021

Bibliographical note

© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.


  • Animals
  • Bone Marrow
  • Hematopoiesis
  • Hematopoietic Stem Cells
  • Mice
  • Mice, Inbred C57BL
  • Purpura, Thrombocytopenic, Idiopathic

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