Bone marrow‐derived myeloid progenitors in the leptomeninges of adult mice,STEM CELLS

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Bone marrow‐derived myeloid progenitors in the leptomeninges of adult mice
STEM CELLS ( IF 4.0 ) Pub Date : 2020-12-03 , DOI: 10.1002/stem.3311
Tobias Koeniger ₁ , Luisa Bell ₁ , Anika Mifka ₂ , Michael Enders ₂ , Valentin Hautmann ₁ , Subba Rao Mekala ₁ , Philipp Kirchner ₃ , Arif B Ekici ₃ , Christian Schulz ₄ , Philipp Wörsdörfer ₁ , Stine Mencl ₅ , Christoph Kleinschnitz ₅ , Süleyman Ergün ₁ , Stefanie Kuerten _{1,

2,

6}

Affiliation

Although the bone marrow contains most hematopoietic activity during adulthood, hematopoietic stem and progenitor cells can be recovered from various extramedullary sites. Cells with hematopoietic progenitor properties have even been reported in the adult brain under steady‐state conditions, but their nature and localization remain insufficiently defined. Here, we describe a heterogeneous population of myeloid progenitors in the leptomeninges of adult C57BL/6 mice. This cell pool included common myeloid, granulocyte/macrophage, and megakaryocyte/erythrocyte progenitors. Accordingly, it gave rise to all major myelo‐erythroid lineages in clonogenic culture assays. Brain‐associated progenitors persisted after tissue perfusion and were partially inaccessible to intravenous antibodies, suggesting their localization behind continuous blood vessel endothelium such as the blood‐arachnoid barrier. Flt3^Cre lineage tracing and bone marrow transplantation showed that the precursors were derived from adult hematopoietic stem cells and were most likely continuously replaced via cell trafficking. Importantly, their occurrence was tied to the immunologic state of the central nervous system (CNS) and was diminished in the context of neuroinflammation and ischemic stroke. Our findings confirm the presence of myeloid progenitors at the meningeal border of the brain and lay the foundation to unravel their possible functions in CNS surveillance and local immune cell production.

中文翻译：

成年小鼠软脑膜中的骨髓源性骨髓祖细胞

虽然骨髓在成年期具有最多的造血活性，但造血干细胞和祖细胞可以从各种髓外部位回收。甚至在稳态条件下在成人大脑中也报道了具有造血祖细胞特性的细胞，但它们的性质和定位仍未得到充分定义。在这里，我们描述了成年 C57BL/6 小鼠软脑膜中髓系祖细胞的异质性群体。该细胞库包括普通髓细胞、粒细胞/巨噬细胞和巨核细胞/红细胞祖细胞。因此，它在克隆形成培养试验中产生了所有主要的骨髓 - 红细胞谱系。脑相关祖细胞在组织灌注后仍然存在，并且部分无法获得静脉抗体，Flt3 ^Cre谱系追踪和骨髓移植表明，前体来源于成体造血干细胞，很可能通过细胞运输不断被替换。重要的是，它们的发生与中枢神经系统 (CNS) 的免疫状态有关，并且在神经炎症和缺血性中风的背景下会减弱。我们的研究结果证实了髓系祖细胞在大脑脑膜边界的存在，并为阐明它们在中枢神经系统监测和局部免疫细胞产生中的可能功能奠定了基础。

更新日期：2021-01-28

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