In situ mapping identifies distinct vascular niches for myelopoiesis.

In situ mapping identifies distinct vascular niches for myelopoiesis.
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原位定位确定骨髓生成的不同血管龛。

DOI:
10.1038/s41586-021-03201-2
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发表时间:
2021-03
期刊:
影响因子:
64.8
通讯作者:
Lucas D
Lucas D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhang J;Wu Q;Johnson CB;Pham G;Kinder JM;Olsson A;Slaughter A;May M;Weinhaus B;D'Alessandro A;Engel JD;Jiang JX;Kofron JM;Huang LF;Prasath VBS;Way SS;Salomonis N;Grimes HL;Lucas D

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与几乎所有其他组织相比,骨髓(BM)中分化的解剖学仍然未知。这是由于缺乏原位检查血细胞产生的策略,这是理解分化、谱系承诺决定和定义空间组织线索如何告知组织功能所必需的。在这里,我们开发的方法来成像骨髓细胞和生成的图集的粒细胞和单核细胞/树突状细胞分化。粒细胞生成和树突/单细胞生成定位于不同的血窦,并显示谱系特异性的空间和克隆结构。急性系统性L.单核细胞增多症感染通过增加的祖细胞自我更新诱导谱系特异性祖细胞簇,但不同的谱系保持空间分离。单核细胞树突状细胞祖细胞(MDP)与Ly 6Clo单核细胞和常规树突状细胞一起定位;这些细胞定位于表达骨髓生成集落刺激因子1(CSF 1/ M-CSF)的主要调节因子的血管亚群。内皮细胞中Csf 1的特异性缺失破坏了MDP周围的结构及其在血窦中的定位。随后,在稳态和感染期间,MDP数量和分化能力降低,Ly 6Clo单核细胞和树突状细胞丢失。这些数据表明,由不同的血管产生的局部线索负责确定性造血的特定空间组织。
In contrast to virtually all other tissues, the anatomy of differentiation in the bone marrow (BM) remains unknown. This is due to a lack of strategies to examine blood cell production in situ, which are required to understand differentiation, lineage commitment decisions, and define how spatial organizing cues inform tissue function. Here we developed approaches to image myelopoiesis and generated atlases of granulocyte and monocyte/dendritic cell differentiation. Granulopoiesis and dendritic/monopoiesis localize to different sinusoids and display lineage-specific spatial and clonal architectures. Acute systemic L. monocytogenes infection induces lineage-specific progenitor clusters through increased progenitor self-renewal, but the different lineages remain spatially separated. Monocyte dendritic cell progenitors (MDP) map with Ly6Clo monocytes and conventional dendritic cells; these localize to a subset of vessels expressing a major regulator of myelopoiesis colony-stimulating-factor 1 (CSF1/ M-CSF). Specific deletion of Csf1 in endothelium disrupted the architecture around MDP and their localization to sinusoids. Subsequently, there were reduced MDP numbers and differentiation ability, and loss of Ly6Clo monocytes and dendritic cells during homeostasis and infection. These data indicate that local cues produced by distinct blood vessels are responsible for specific spatial organization of definitive hematopoiesis.
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