Deciphering human macrophage development at single-cell resolution

Zhilei Bian, Yandong Gong, Tao Huang, Christopher Z. W. Lee, Lihong Bian, Zhijie Bai, Hui Shi, Yang Zeng, Chen Liu, Jian He, Jie Zhou, Xianlong Li, Zongcheng Li, Yanli Ni, Chunyu Ma, Lei Cui, Rui Zhang, Jerry K. Y. Chan, Lai Guan Ng, Yu Lan (), Florent Ginhoux () and Bing Liu ()
Additional contact information
Zhilei Bian: Jinan University
Yandong Gong: Academy of Military Sciences
Tao Huang: Academy of Military Sciences
Christopher Z. W. Lee: Technology and Research (A*STAR), BIOPOLIS
Lihong Bian: Fifth Medical Center of Chinese PLA General Hospital
Zhijie Bai: Academy of Military Sciences
Hui Shi: Academy of Military Sciences
Yang Zeng: Fifth Medical Center of Chinese PLA General Hospital
Chen Liu: Academy of Military Sciences
Jian He: Academy of Military Sciences
Jie Zhou: Fifth Medical Center of Chinese PLA General Hospital
Xianlong Li: Academy of Military Sciences
Zongcheng Li: Fifth Medical Center of Chinese PLA General Hospital
Yanli Ni: Fifth Medical Center of Chinese PLA General Hospital
Chunyu Ma: Fifth Medical Center of Chinese PLA General Hospital
Lei Cui: Capital Medical University, National Center for Children’s Health
Rui Zhang: Capital Medical University
Jerry K. Y. Chan: KK Women’s and Children’s Hospital
Lai Guan Ng: Technology and Research (A*STAR), BIOPOLIS
Yu Lan: Jinan University
Florent Ginhoux: Technology and Research (A*STAR), BIOPOLIS
Bing Liu: Jinan University

Nature, 2020, vol. 582, issue 7813, 571-576

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41586-020-2316-7

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