Deciphering human macrophage development at single-cell resolution

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Deciphering human macrophage development at single-cell resolution
Deciphering human macrophage development at single-cell resolution
Journal Title:
Publication Date:
20 May 2020
Bian Z, Gong Y, Huang T, Lee CZW, Bian L, Bai Z, Shi H, Zeng Y, Liu C, He J, Zhou J, Li X, Li Z, Ni Y, Ma C, Cui L, Zhang R, Chan JKY, Ng LG, Lan Y, Ginhoux F, Liu B. Deciphering Human Macrophage Development at Single-Cell Resolution. Nature. 2020 May 20. volume 582, pages 571–576(2020)
Macrophages are the first cells of the nascent immune system to emerge during embryonic development. In mice, embryonic macrophages infiltrate developing organs, where they differentiate symbiotically into tissue-resident macrophages (TRMs)1. However, our understanding of the origins and specialization of macrophages in human embryos is limited. Here we isolated CD45+ haematopoietic cells from human embryos at Carnegie stages 11 to 23 and subjected them to transcriptomic profiling by single-cell RNA sequencing, followed by functional characterization of a population of CD45+CD34+CD44+ yolk sac-derived myeloid-biased progenitors (YSMPs) by single-cell culture. We also mapped macrophage heterogeneity across multiple anatomical sites and identified diverse subsets, including various types of embryonic TRM (in the head, liver, lung and skin). We further traced the specification trajectories of TRMs from either yolk sac-derived primitive macrophages or YSMP-derived embryonic liver monocytes using both transcriptomic and developmental staging information, with a focus on microglia. Finally, we evaluated the molecular similarities between embryonic TRMs and their adult counterparts. Our data represent a comprehensive characterization of the spatiotemporal dynamics of early macrophage development during human embryogenesis, providing a reference for future studies of the development and function of human TRMs.
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Funding Info:
This research / project is supported by the Singapore National Research Foundation - Singapore National Research Foundation Senior Investigatorship
Grant Reference no. : NRF2016NRF-NRFI001-02

This research is supported by core funding from: Singapore Immunology Network
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