DICP OpenIR
Multiplexed, Sequential Secretion Analysis of the Same Single Cells Reveals Distinct Effector Response Dynamics Dependent on the Initial Basal State
Chen, Zhuo1; Lu, Yao1,2; Zhang, Kerou1; Xiao, Yang1; Lu, Jun3,4; Fan, Rong1,3,4,5
Corresponding AuthorLu, Yao(luyao@dicp.ac.cn) ; Fan, Rong(rong.fan@yale.edu)
Keywordheterogeneity macrophage activation sequential analysis single-cell cytokine assay single-cell RNA sequencing
Source PublicationADVANCED SCIENCE
2019-05-03
ISSN2198-3844
DOI10.1002/advs.201801361
Volume6Issue:9Pages:11
Funding ProjectNational 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
Funding OrganizationNational 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
WOS SubjectChemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science
WOS KeywordCD8(+) T-CELLS ; HETEROGENEITY ; EXPRESSION ; IMMUNE ; TECHNOLOGIES ; ACTIVATION ; PROTECTION ; CYTOMETRY
AbstractThe 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.
Language英语
Funding OrganizationNational 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
WOS IDWOS:000467524500019
PublisherWILEY
Citation statistics
Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/165477
Collection中国科学院大连化学物理研究所
Corresponding AuthorLu, Yao; Fan, Rong
Affiliation1.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
Recommended Citation
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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