Splenic hematopoiesis is crucial to the pathogenesis of diseases including myocardial infarction and atherosclerosis. The spleen acts as a reservoir of myeloid cells, which are quickly expelled out in response to acute inflammation. In contrast to the well-defined bone marrow hematopoiesis, the cellular and molecular components sustaining splenic hematopoiesis are poorly understood. Surprisingly, we found that, unlike quiescent bone marrow hematopoietic stem cells (HSC), most of splenic HSC are in the G1 phase in C57BL/6 mice. Moreover, splenic HSC were enriched for genes involved in G0-G1 transition and expressed lower levels of genes responsible for G1-S transition. These data indicate that, at steady state, splenic HSC are pre-activated, which may expedite their cell cycle entry in emergency conditions. Consistently, in the acute phase of septic shock induced by LPS injection, splenic HSC entered the S-G2-M phase, whereas bone marrow HSC did not. Mobilization and transplantation experiments displayed that bone marrow HSC, once in the spleen, acquired cell cycle status similar to splenic HSC, strongly suggesting that the splenic microenvironment plays an important role in HSC pre-activation. In addition, we found that myeloid translocation gene 16 (Mtg16) deficiency in C57BL/6 mice resulted in significantly increased S-G2-M entry of splenic but not bone marrow HSC, suggesting that Mtg16 is an intrinsic negative regulator of G1-S transition in splenic HSC. Altogether, this study demonstrates that compared to bone marrow, splenic HSC are in a pre-activated state, which is driven by extracellular signals provided by splenic microenvironment and HSC intrinsic factor Mtg16.

中文翻译：

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脾脏造血干细胞表现出预激活的表型。


脾脏造血对于心肌梗塞、动脉粥样硬化等疾病的发病机制至关重要。脾脏充当骨髓细胞的储存库，这些细胞会因急性炎症而迅速排出。与明确的骨髓造血相反，维持脾造血的细胞和分子成分却知之甚少。令人惊讶的是，我们发现，与静止的骨髓造血干细胞（HSC）不同，C57BL/6小鼠中大部分脾脏HSC处于G1期。此外，脾HSC富含参与G0-G1转变的基因，并且表达较低水平的负责G1-S转变的基因。这些数据表明，在稳定状态下，脾脏 HSC 被预先激活，这可能会加速它们在紧急情况下进入细胞周期。一致地，在LPS注射引起的感染性休克的急性期，脾脏HSC进入S-G2-M期，而骨髓HSC则没有。动员和移植实验表明，骨髓HSC一旦进入脾脏，就获得了与脾脏HSC相似的细胞周期状态，强烈表明脾脏微环境在HSC预激活中发挥着重要作用。此外，我们发现 C57BL/6 小鼠中骨髓易位基因 16 (Mtg16) 缺陷导致脾脏 HSC 的 S-G2-M 进入显着增加，但骨髓 HSC 没有显着增加，表明 Mtg16 是 G1-S 转变的内在负调节因子在脾 HSC 中。总之，这项研究表明，与骨髓相比，脾脏 HSC 处于预激活状态，这是由脾微环境和 HSC 内因子 Mtg16 提供的细胞外信号驱动的。