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Multiplexed, Sequential Secretion Analysis of the Same Single Cells Reveals Distinct Effector Response Dynamics Dependent on the Initial Basal State

文献类型：期刊论文

作者Chen, Zhuo1; Lu, Yao1,2; Zhang, Kerou1; Xiao, Yang1; Lu, Jun3,4; Fan, Rong1,3,4,5
刊名ADVANCED SCIENCE
出版日期2019-05-03
卷号6期号:9页码:11
关键词heterogeneity macrophage activation sequential analysis single-cell cytokine assay single-cell RNA sequencing
ISSN号2198-3844
DOI10.1002/advs.201801361
通讯作者Lu, Yao(luyao@dicp.ac.cn) ; Fan, Rong(rong.fan@yale.edu)
英文摘要The effector response of immune cells dictated by an array of secreted proteins is a highly dynamic process, requiring sequential measurement of all relevant proteins from single cells. Herein, a microchip-based, 10-plexed, sequential secretion assay on the same single cells and at the scale of approximate to 5000 single cells measured simultaneously over 4 time points are shown. It is applied to investigating the time course of single human macrophage response to toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) and reveals four distinct activation modes for different proteins in single cells. Protein secretion dynamics classifies the cells into two major activation states dependent on the basal state of each cell. Single-cell RNA sequencing performed on the same samples at the matched time points further demonstrates the existence of two major activation states at the transcriptional level, which are enriched for translation versus inflammatory programs, respectively. These results show a cell-intrinsic heterogeneous response in a phenotypically homogeneous cell population. This work demonstrates the longitudinal tracking of protein secretion signature in thousands of single cells at multiple time points, providing dynamic information to better understand how individual immune cells react to pathogenic challenges over time and how they together constitute a population response.
WOS关键词CD8(+) T-CELLS ; HETEROGENEITY ; EXPRESSION ; IMMUNE ; TECHNOLOGIES ; ACTIVATION ; PROTECTION ; CYTOMETRY
资助项目National Institutes of Health (NIH)[U54CA193461] ; National Institutes of Health (NIH)[R33CA196411] ; National Institutes of Health (NIH)[U01DK104331] ; National Institutes of Health (NIH)[U54CA209992] ; National Institutes of Health (NIH)[7297] ; National Institutes of Health (NIH)[R21CA177393] ; National Science Foundation CAREER Award[CBET-1351443] ; NIH[R01CA149109] ; NIH[R01GM116855] ; Connecticut RMRF grant[15-RMB-YALE-06] ; Sackler Institute Research Grant ; NIDDK
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:000467524500019
出版者WILEY
资助机构National Institutes of Health (NIH) ; National Institutes of Health (NIH) ; National Science Foundation CAREER Award ; National Science Foundation CAREER Award ; NIH ; NIH ; Connecticut RMRF grant ; Connecticut RMRF grant ; Sackler Institute Research Grant ; Sackler Institute Research Grant ; NIDDK ; NIDDK ; National Institutes of Health (NIH) ; National Institutes of Health (NIH) ; National Science Foundation CAREER Award ; National Science Foundation CAREER Award ; NIH ; NIH ; Connecticut RMRF grant ; Connecticut RMRF grant ; Sackler Institute Research Grant ; Sackler Institute Research Grant ; NIDDK ; NIDDK ; National Institutes of Health (NIH) ; National Institutes of Health (NIH) ; National Science Foundation CAREER Award ; National Science Foundation CAREER Award ; NIH ; NIH ; Connecticut RMRF grant ; Connecticut RMRF grant ; Sackler Institute Research Grant ; Sackler Institute Research Grant ; NIDDK ; NIDDK ; National Institutes of Health (NIH) ; National Institutes of Health (NIH) ; National Science Foundation CAREER Award ; National Science Foundation CAREER Award ; NIH ; NIH ; Connecticut RMRF grant ; Connecticut RMRF grant ; Sackler Institute Research Grant ; Sackler Institute Research Grant ; NIDDK ; NIDDK
源URL[http://cas-ir.dicp.ac.cn/handle/321008/165476]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Lu, Yao; Fan, Rong
作者单位1.Yale Univ, Dept Biomed Engn, New Haven, CT 06520 USA
2.Chinese Acad Sci, Dalian Inst Chem Phys, Dept Biotechnol, Dalian 116023, Liaoning, Peoples R China
3.Yale Sch Med, Dept Genet, New Haven, CT 06520 USA
4.Yale Stem Cell Ctr, New Haven, CT 06520 USA
5.Yale Canc Ctr, New Haven, CT 06520 USA
推荐引用方式
GB/T 7714		 Chen, Zhuo,Lu, Yao,Zhang, Kerou,et al. Multiplexed, Sequential Secretion Analysis of the Same Single Cells Reveals Distinct Effector Response Dynamics Dependent on the Initial Basal State[J]. ADVANCED SCIENCE,2019,6(9):11.
APA Chen, Zhuo,Lu, Yao,Zhang, Kerou,Xiao, Yang,Lu, Jun,&Fan, Rong.(2019).Multiplexed, Sequential Secretion Analysis of the Same Single Cells Reveals Distinct Effector Response Dynamics Dependent on the Initial Basal State.ADVANCED SCIENCE,6(9),11.
MLA Chen, Zhuo,et al."Multiplexed, Sequential Secretion Analysis of the Same Single Cells Reveals Distinct Effector Response Dynamics Dependent on the Initial Basal State".ADVANCED SCIENCE 6.9(2019):11.

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来源：大连化学物理研究所

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