Hematopoietic Stem Cell Requirement for Macrophage Regeneration Is Tissue Specific.

Hematopoietic Stem Cell Requirement for Macrophage Regeneration Is Tissue Specific.
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巨噬细胞再生对造血干细胞的需求是组织特异性的。

DOI:
10.4049/jimmunol.2100344
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发表时间:
2021-12-15
影响因子:
4.4
通讯作者:
Ghosn, Eliver Eid Bou
Ghosn, Eliver Eid Bou
中科院分区:
医学2区
文献类型:
--
作者:
Eddins, Devon J.;Kosters, Astrid;Waters, Jeffrey;Sosa, Jasmine;Phillips, Megan;Yadava, Koshika;Herzenberg, Leonore A.;Kuipers, Hedwich F.;Ghosn, Eliver Eid Bou

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组织驻留巨噬细胞(TRMΦ)是重要的免疫哨兵,负责维持其特定生态位内的组织和免疫稳态。最近,TRMΦ的起源经历了严格的审查,现在大多数TRMΦ被认为是在胚胎发育早期独立于造血干细胞(HSC)的起源。我们先前表征了两种不同的小鼠腹腔巨噬细胞亚群(分别为大和小腹膜巨噬细胞; LPM和SPM),其起源和与胎儿和成人长期(LT)-HSC的关系尚未得到充分研究。在这里,我们采用高度纯化的LT-HSC移植和体内谱系追踪,以显示LPM和SPM的双重个体发育,其中腹膜巨噬细胞的初始波是从卵黄囊衍生的前体接种的,随后需要LT-HSC进行再生。相比之下,移植的胎儿和成人LT-HSC不能再生脑驻留小胶质细胞。因此,我们证明LT-HSC保留了发育成TRMΦ的潜力,但它们的需求在腹膜和脑中是组织特异性的。
Tissue-resident macrophages (TRMΦ) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRMΦ have undergone intense scrutiny where now most TRMΦ are thought to originate early during embryonic development independent of hematopoietic stem cells (HSCs). We previously characterized two distinct subsets of mouse peritoneal cavity macrophages (Large and Small Peritoneal Macrophages; LPM and SPM, respectively) whose origins and relationship to both fetal and adult long-term (LT)-HSCs have not been fully investigated. Here we employ highly purified LT-HSC transplantation and in vivo lineage tracing to show a dual ontogeny for LPM and SPM, where the initial wave of peritoneal macrophages is seeded from yolk sac-derived precursors, which later require LT-HSCs for regeneration. In contrast, transplanted fetal and adult LT-HSCs are not able to regenerate brain-resident microglia. Thus, we demonstrate that LT-HSCs retain the potential to develop into TRMΦ, but their requirement is tissue-specific in the peritoneum and brain.
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