A perisinusoidal niche for extramedullary haematopoiesis in the spleen.
A perisinusoidal niche for extramedullary haematopoiesis in the spleen.
复制标题
DOI：
10.1038/nature15530
复制
发表时间：
2015-11-26
期刊：
影响因子：
64.8
通讯作者：
Morrison SJ
中科院分区：
文献类型：
--
作者：
Inra CN;Zhou BO;Acar M;Murphy MM;Richardson J;Zhao Z;Morrison SJ
造血应激调动造血干细胞（hsc）从骨髓转移到脾脏，诱导髓外造血（EMH）。然而，EMH生态位的细胞性质尚不清楚。在这里，我们评估了骨髓消融、失血或妊娠诱导EMH后小鼠脾脏中关键生态位因子SCF和CXCL12的来源。在每种情况下，Scf主要由内皮细胞和Tcf21+基质细胞表达，主要在红髓窦周围表达，而Cxcl12则由Tcf21+基质细胞的一个亚群表达。EMH通过诱导内皮细胞和基质细胞增殖，使表达scf的内皮细胞和基质细胞扩增。多数脾造血干细胞毗邻红髓Tcf21+基质细胞。有条件地删除脾内皮细胞中的Scf或Tcf21+基质细胞中的Scf或Cxcl12，严重降低脾脏EMH和血细胞计数，但不影响骨髓造血。因此，内皮细胞和Tcf21+基质细胞在脾脏中创造了一个窦周EMH生态位，这是对各种造血应激的生理反应所必需的。
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 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 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.