Bone marrow remodeling supports hematopoiesis in response to immune thrombocytopenia progression in mice.
Bone marrow remodeling supports hematopoiesis in response to immune thrombocytopenia progression in mice.
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骨髓重塑支持小鼠的免疫血小板减少进展。
DOI：
10.1182/bloodadvances.2020003887
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发表时间：
2021-12-14
期刊：
影响因子：
7.5
通讯作者：
Hitchcock, Ian S.
中科院分区：
文献类型：
--
作者：
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.
持续ITP激活并增加功能性lt - hsc的数量。重建的ITP骨髓增强造血功能。免疫性血小板减少症（ITP）是一种获得性自身免疫性疾病，其特征是血小板产生减少和免疫系统持续攻击破坏功能正常的血小板。然而，延长ITP对更不成熟的造血祖细胞的影响仍然是一个开放的研究领域。通过使用小鼠体内扩展ITP模型，我们发现ITP的进展可驱动相当大的祖细胞扩增和骨髓（BM）重塑。使用Lin-Sca1 +c-Kit+ CD48-CD150 +长期造血干细胞（LT-HSC）进行的单细胞试验显示，LT-HSC的体外活化和增殖水平升高。然而，通过体内连续移植测量，激活增加并不以牺牲LT-HSC功能为代价。ITP进展与BM血管舒张和血管生成以及CXCL12的局部产生增加两倍有关，CXCL12是LT-HSC功能和BM归巢所必需的细胞因子，在LepR+ BM基质细胞中高水平表达。这与LepR+ BM基质细胞增加1.5倍和祖细胞归巢到BM的5.5倍相关。间质细胞的增加是短暂的，在血小板计数恢复正常后恢复到基线水平，但基底膜的血管变化持续存在。总之，我们的数据表明，LT-HSC在ITP的作用下会扩增，并且LT-HSC在持续造血应激期间的功能是通过适应性BM微环境来维持的。
Sustained ITP activates and increases the number of functional LT-HSCs. The remodeled ITP bone marrow enhances hematopoiesis. 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.
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影响因子：
5.9
作者：
Famili F;Brugman MH;Taskesen E;Naber BEA;Fodde R;Staal FJT
通讯作者：
Staal FJT
影响因子：
64.5
作者：
Baryawno, Ninib;Przybylski, Dariusz;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
21.3
作者：
Decker M;Martinez-Morentin L;Wang G;Lee Y;Liu Q;Leslie J;Ding L
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Ding L
影响因子：
21.3
作者：
Asada N;Kunisaki Y;Pierce H;Wang Z;Fernandez NF;Birbrair A;Ma'ayan A;Frenette PS
通讯作者：
Frenette PS
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ