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A bifurcation concept for B-lymphoid/plasmacytoid dendritic cells with largely fluctuating transcriptome dynamics

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 t...

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Published in:Cell reports (Cambridge) 2022-08, Vol.40 (9), p.111260-111260, Article 111260
Main Authors: Nagaharu, Keiki, Kojima, Yasuhiro, Hirose, Haruka, Minoura, Kodai, Hinohara, Kunihiko, Minami, Hirohito, Kageyama, Yuki, Sugimoto, Yuka, Masuya, Masahiro, Nii, Shigeru, Seki, Masahide, Suzuki, Yutaka, Tawara, Isao, Shimamura, Teppei, Katayama, Naoyuki, Nishikawa, Hiroyoshi, Ohishi, Kohshi
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Language:English
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Summary: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. [Display omitted] •Human B and plasmacytoid DCs have common progenitors•B/pDC bifurcation is a hotspot of large fluctuating transcriptome dynamics•LFA-1 is a key molecule associated with pDC-directed cells in dry and wet approaches•A fluctuation-based concept is proposed for hematopoietic differentiation Nagaharu et al. show that human B-lymphoid and plasmacytoid DCs have common progenitors with a “hotspot” of large fluctuating transcriptome dynamics, in association of LFA-1 expression with pDC differentiation bias, using dry/wet approaches. They propose a fluctuation-based concept of hematopoietic differentiation that reconciles continuous and discrete models.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.111260