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Ly6DSiglec-H 前体通过 Zbtb46Ly6D 中间阶段促进常规树突状细胞的产生。

Ly6DSiglec-H precursors contribute to conventional dendritic cells via a Zbtb46Ly6D intermediary stage.

机构信息

Institute for Immunology, Biomedical Center, LMU Munich, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany.

Institute for Experimental Neuroimmunology, Technical University of Munich, School of Medicine, Ismaninger Str. 22, 81675, Munich, Germany.

出版信息

Nat Commun. 2022 Jun 16;13(1):3456. doi: 10.1038/s41467-022-31054-4.

DOI:10.1038/s41467-022-31054-4
PMID:35705536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9200809/
Abstract

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 CD11cMHCIISiglec-HCCR9 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 CD11cMHCIISiglec-HCCR9 DC precursor pool cells expressing high levels of Ly6D and lacking expression of transcription factor Zbtb46 contain CCR9B220 immediate pDC precursors and CCR9B220 (lo-lo) cells which still generate pDCs and cDCs in vitro and in vivo under steady state conditions. cDC-primed cells within the Ly6DZbtb46 lo-lo precursors rapidly upregulate Zbtb46 and pass through a Zbtb46Ly6D 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 Zbtb46Ly6D 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.

摘要

浆细胞样和经典树突状细胞 (pDC 和 cDC) 由骨髓中的祖细胞生成，pDC 或 cDC 亚型的定向分化可能发生在更早或更晚的祖细胞阶段。在小鼠骨髓的 CD11cMHCIISiglec-HCCR9 DC 前体细胞群中，细胞可以同时生成 pDC 和 cDC。在这里，我们通过单细胞转录组学和高维流式细胞术结合细胞命运分析来研究该细胞群的异质性和定向分化：在 CD11cMHCIISiglec-HCCR9 DC 前体细胞群中，表达高水平 Ly6D 且缺乏转录因子 Zbtb46 表达的细胞包含 CCR9B220 立即型 pDC 前体和 CCR9B220（lo-lo）细胞，在稳态条件下，这些细胞在体外和体内仍能生成 pDC 和 cDC。在 Ly6DZbtb46 lo-lo 前体中的 cDC 前体细胞迅速上调 Zbtb46，并在细胞分裂后获得 cDC 表型之前通过 Zbtb46Ly6D 中间阶段。I 型 IFN 刺激通过阻止 cDC 前体细胞在 Zbtb46Ly6D 阶段的扩增和分化为 cDC，从而限制 cDC 并促进该前体细胞群中 pDC 的产生。外部因素对前体细胞中 pDC 与 cDC 输出的调节可能允许在后期分化阶段适应 DC 亚群组成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/d517a64b22bf/41467_2022_31054_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/961c3c0e27bf/41467_2022_31054_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/0fab3764a2a2/41467_2022_31054_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/61d072618250/41467_2022_31054_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/466b2eabca34/41467_2022_31054_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/ba7d180eeac6/41467_2022_31054_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/d517a64b22bf/41467_2022_31054_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/961c3c0e27bf/41467_2022_31054_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/0fab3764a2a2/41467_2022_31054_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/61d072618250/41467_2022_31054_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/466b2eabca34/41467_2022_31054_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/ba7d180eeac6/41467_2022_31054_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/9200809/d517a64b22bf/41467_2022_31054_Fig6_HTML.jpg

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