Ly6D(+)Siglec-H(+) precursors contribute to conventional dendritic cells via a Zbtb46(+)Ly6D(+) intermediary stage.

Ly6D(+)Siglec-H(+) precursors contribute to conventional dendritic cells via a Zbtb46(+)Ly6D(+) intermediary stage.
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DOI:
10.1038/s41467-022-31054-4
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发表时间:
2022-06-16
影响因子:
16.6
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中科院分区:
综合性期刊1区
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浆细胞样细胞和常规树突状细胞(pDC和cDC)是由骨髓中的祖细胞产生的,向pDC或cDC亚型的转移可能发生在祖细胞早期和晚期。小鼠骨髓的CD11c+MHCII−/ losiglece - h +CCR9lo DC前体部分内的细胞产生pDCs和cdc。在CD11c+MHCII−/ losiglece - h +CCR9lo DC前体池中,表达高水平Ly6D且转录因子Zbtb46缺乏表达的细胞含有CCR9loB220hi直接pDC前体,而CCR9loB220lo (lo-lo)细胞在体外和体内稳态条件下仍能生成pDC和cdc。在Ly6DhiZbtb46 - lo-lo前体内的cDC-引物细胞迅速上调Zbtb46,并在细胞分裂后获得cDC表型之前经过Zbtb46+Ly6D+中间阶段。I型IFN刺激限制了cDC,并通过将cDC启动的细胞阻止在Zbtb46+Ly6D+阶段来促进pDC的输出,从而阻止它们扩展和分化为cDC。外部因素对前体pDC和cDC输出的调制可能允许在分化后期调整DC子集组成。传统树突状细胞和浆细胞样树突状细胞(DC)的个体发生以及这两种细胞类型之间的关系尚不完全清楚。在这里,作者鉴定了一组表达Ly6D siglece - h和Zbtb46的骨髓前体细胞,它们可以分化为cDC或pDC,并表明I型IFN可以限制cDC并促进这些前体细胞的pDC输出。
Plasmacytoid and conventional dendritic cells (pDC and cDC) are generated from progenitor cells in the bone marrow and commitment to pDCs or cDC subtypes may occur in earlier and later progenitor stages. Cells within the CD11c+MHCII−/loSiglec-H+CCR9lo DC precursor fraction of the mouse bone marrow generate both pDCs and cDCs. Here we investigate the heterogeneity and commitment of subsets in this compartment by single-cell transcriptomics and high-dimensional flow cytometry combined with cell fate analysis: Within the CD11c+MHCII−/loSiglec-H+CCR9lo DC precursor pool cells expressing high levels of Ly6D and lacking expression of transcription factor Zbtb46 contain CCR9loB220hi immediate pDC precursors and CCR9loB220lo (lo-lo) cells which still generate pDCs and cDCs in vitro and in vivo under steady state conditions. cDC-primed cells within the Ly6DhiZbtb46– lo-lo precursors rapidly upregulate Zbtb46 and pass through a Zbtb46+Ly6D+ intermediate stage before acquiring cDC phenotype after cell division. Type I IFN stimulation limits cDC and promotes pDC output from this precursor fraction by arresting cDC-primed cells in the Zbtb46+Ly6D+ stage preventing their expansion and differentiation into cDCs. Modulation of pDC versus cDC output from precursors by external factors may allow for adaptation of DC subset composition at later differentiation stages. The ontogeny of conventional and plasmacytoid dendritic cells (DC) and how these two cell types are related is not fully known. Here the authors identify a pool of bone marrow precursor cells expressing Ly6D Siglec-H and Zbtb46 that can differentiate into either cDC or pDC and show that type I IFN can limit cDC and favor pDC output from these precursors.
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