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Bone marrow remodeling supports hematopoiesis in response to immune thrombocytopenia progression in mice
| Content Provider | Scilit |
|---|---|
| Author | Herd, Oliver J. Rani, Gulab Fatima Hewitson, James P. Hogg, Karen Stone, Andrew P. Cooper, Nichola Kent, David G. Genever, Paul G. Hitchcock, Ian S. |
| Copyright Year | 2021 |
| Description | 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. |
| Related Links | https://ashpublications.org/bloodadvances/article-pdf/doi/10.1182/bloodadvances.2020003887/1819176/bloodadvances.2020003887.pdf |
| Ending Page | 4889 |
| Page Count | 13 |
| Starting Page | 4877 |
| DOI | 10.1182/bloodadvances.2020003887 |
| Journal | Blood advances |
| Issue Number | 23 |
| Volume Number | 5 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2021-11-24 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Hematopoietic Functionality Bone Marrow Platelet Itp Stromal Remodeling Adapting Journal: Blood advances (Vol- 136, Issue- 23) |
| Content Type | Text |
| Resource Type | Article |
