A bifurcation concept for B-lymphoid/plasmacytoid dendritic cells with largely fluctuating transcriptome dynamics.
A bifurcation concept for B-lymphoid/plasmacytoid dendritic cells with largely fluctuating transcriptome dynamics.
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DOI：
10.1016/j.celrep.2022.111260
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发表时间：
2022-08
期刊：
影响因子：
8.8
通讯作者：
Keiki Nagaharu;Yasuhiro Kojima;Haruka Hirose;Kodai Minoura;Kunihiko Hinohara;Hirohito Minami;Y. Kageyama;Y. Sugimoto;M. Masuya;Shigeru Nii;Masahide Seki;Yutaka Suzuki;I. Tawara;Teppei Shimamura;N. Katayama;Hiroyoshi Nishikawa;K. Ohishi
中科院分区：
文献类型：
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作者：
Keiki Nagaharu;Yasuhiro Kojima;Haruka Hirose;Kodai Minoura;Kunihiko Hinohara;Hirohito Minami;Y. Kageyama;Y. Sugimoto;M. Masuya;Shigeru Nii;Masahide Seki;Yutaka Suzuki;I. Tawara;Teppei Shimamura;N. Katayama;Hiroyoshi Nishikawa;K. Ohishi
造血被认为是一个分层的逐步过程，但在单细胞RNA测序后被修改为一个连续的过程。然而，分化过程中单细胞转录组动力学的不确定性或波动并未被考虑在内，淋巴细胞背景下的树突状细胞（DC）途径仍不清楚。在这里，我们通过干法和湿法确定了人B浆细胞样DC （pDC）分叉在假定的B/NK祖细胞区域的大波动转录组动力学。通过在深度生成模型中将剪接动力学转换为扩散动力学，我们的原始计算方法揭示了IL-7Rα+区域的B/pDC分岔处的强波动，并且LFA-1在分岔处的pDC方向上呈正波动。这些预期被IL-7Rα+部分中B/pDC祖细胞的存在和LFA-1在pDC偏向祖细胞中的优先表达所证实。我们提供了一个基于波动的分化模型，它调和了连续和离散模型，并适用于其他发展系统。
Hematopoiesis was considered a hierarchical stepwise process but was revised to a continuous process following single-cell RNA sequencing. However, the uncertainty or fluctuation of single-cell transcriptome dynamics during differentiation was not considered, and the dendritic cell (DC) pathway in the lymphoid context remains unclear. Here, we identify human B-plasmacytoid DC (pDC) bifurcation as large fluctuating transcriptome dynamics in the putative B/NK progenitor region by dry and wet methods. By converting splicing kinetics into diffusion dynamics in a deep generative model, our original computational methodology reveals strong fluctuation at B/pDC bifurcation in IL-7Rα+regions, and LFA-1 fluctuates positively in the pDC direction at the bifurcation. These expectancies are validated by the presence of B/pDC progenitors in the IL-7Rα+fraction and preferential expression of LFA-1 in pDC-biased progenitors with a niche-like culture system. We provide a model of fluctuation-based differentiation, which reconciles continuous and discrete models and is applicable to other developmental systems.