Continuous single cell imaging reveals sequential steps of plasmacytoid dendritic cell development from common dendritic cell progenitors
Continuous single cell imaging reveals sequential steps of plasmacytoid dendritic cell development from common dendritic cell progenitors
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DOI：
10.1038/srep37462
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发表时间：
2016-11-28
影响因子：
4.6
通讯作者：
Krug, Anne B.
中科院分区：
文献类型：
--
作者：
Dursun, Ezgi;Endele, Max;Krug, Anne B.
功能不同的浆细胞样和常规树突状细胞（pDC和cDC）形成先天性和适应性免疫。它们来源于鼠骨髓中常见的树突状细胞祖细胞（CDPs），其产生CD 11 c（+）MHCII-前体，并早期定型为DC亚群。在这项研究中，我们通过连续单细胞成像和跟踪监测CDP培养物中CD 11 c、MHC II类、Siglec H和CCR 9的表达，将CDP的pDC发育分解为有序的分化事件序列。CDP谱系的分析揭示了CDP在部分CDP集落中逐步分化为pDC。该发育途径涉及早期CD 11 c（+）SiglecH（-）pre-DC阶段和Siglec H+ CCR 9（低）前体阶段，随后迅速上调CCR 9，表明最终pDC分化。然而，在大多数剩余CDP谱系中，Siglec H+ CCR 9（低）前体状态维持了几代。因此，尽管一部分CDP快速地过渡通过前体阶段以产生第一波pDC，但大多数CDP后代分化更慢并产生更长寿命的前体细胞，其准备按需分化。
Functionally distinct plasmacytoid and conventional dendritic cells (pDC and cDC) shape innate and adaptive immunity. They are derived from common dendritic cell progenitors (CDPs) in the murine bone marrow, which give rise to CD11c(+) MHCII- precursors with early commitment to DC subpopulations. In this study, we dissect pDC development from CDP into an ordered sequence of differentiation events by monitoring the expression of CD11c, MHC class II, Siglec H and CCR9 in CDP cultures by continuous single cell imaging and tracking. Analysis of CDP genealogies revealed a stepwise differentiation of CDPs into pDCs in a part of the CDP colonies. This developmental pathway involved an early CD11c(+) SiglecH(-) pre-DC stage and a Siglec H+ CCR9(low) precursor stage, which was followed rapidly by upregulation of CCR9 indicating final pDC differentiation. In the majority of the remaining CDP pedigrees however the Siglec H+ CCR9(low) precursor state was maintained for several generations. Thus, although a fraction of CDPs transits through precursor stages rapidly to give rise to a first wave of pDCs, the majority of CDP progeny differentiate more slowly and give rise to longer lived precursor cells which are poised to differentiate on demand.