Thymic macrophages consist of two populations with distinct localization and origin.
Thymic macrophages consist of two populations with distinct localization and origin.
复制标题
胸腺巨噬细胞由两个具有不同定位和起源的人群组成。
DOI：
10.7554/elife.75148
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发表时间：
2022-11-30
期刊：
影响因子：
7.7
通讯作者：
Dzhagalov IL
中科院分区：
文献类型：
--
作者：
Zhou TA;Hsu HP;Tu YH;Cheng HK;Lin CY;Chen NJ;Tsai JW;Robey EA;Huang HC;Hsu CL;Dzhagalov IL
组织驻留巨噬细胞对于保护免受病原体入侵和维持器官内稳态是必不可少的。胸腺巨噬细胞吞噬凋亡胸腺细胞的能力是很好的赞赏，但很少有人知道他们的个体发育，维护和多样性。在这里，我们表征了这些细胞的表面表型和转录谱，并定义了它们的表达特征。胸腺巨噬细胞与脾红髓巨噬细胞和枯否细胞的关系最为密切，并且与这些细胞共享转录因子（TF）SpiC的表达。单细胞RNA测序（scRNA-Seq）显示，成年胸腺中的巨噬细胞由两个群体组成，其特征在于Timd 4和Cx 3cr 1的表达。值得注意的是，Timd 4+细胞位于皮质，而Cx 3cr 1+巨噬细胞仅限于髓质和皮质-髓质交界处。使用盾嵌合体，胚胎胸腺移植和遗传命运作图，我们发现，这两个群体有不同的起源。Timd 4+胸腺巨噬细胞是胚胎来源的，而Cx 3cr 1+巨噬细胞来源于成体造血干细胞。衰老对胸腺中的巨噬细胞有着深远的影响。Timd 4+细胞经历逐渐磨损，而Cx 3cr 1+细胞随着年龄的增长而缓慢积累，在老年小鼠中，是胸腺中占主导地位的巨噬细胞群体。总之，我们的工作定义了胸腺巨噬细胞的表型，起源和多样性。
Tissue-resident macrophages are essential to protect from pathogen invasion and maintain organ homeostasis. The ability of thymic macrophages to engulf apoptotic thymocytes is well appreciated, but little is known about their ontogeny, maintenance, and diversity. Here, we characterized the surface phenotype and transcriptional profile of these cells and defined their expression signature. Thymic macrophages were most closely related to spleen red pulp macrophages and Kupffer cells and shared the expression of the transcription factor (TF) SpiC with these cells. Single-cell RNA sequencing (scRNA-Seq) showed that the macrophages in the adult thymus are composed of two populations distinguished by the expression of Timd4 and Cx3cr1. Remarkably, Timd4+ cells were located in the cortex, while Cx3cr1+ macrophages were restricted to the medulla and the cortico-medullary junction. Using shield chimeras, transplantation of embryonic thymuses, and genetic fate mapping, we found that the two populations have distinct origins. Timd4+ thymic macrophages are of embryonic origin, while Cx3cr1+ macrophages are derived from adult hematopoietic stem cells. Aging has a profound effect on the macrophages in the thymus. Timd4+ cells underwent gradual attrition, while Cx3cr1+ cells slowly accumulated with age and, in older mice, were the dominant macrophage population in the thymus. Altogether, our work defines the phenotype, origin, and diversity of thymic macrophages.