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Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection

Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular beha... Full description

Journal Title: Nature medicine 2020-04, Vol.26 (4), p.511-518
Main Author: Kazer, Samuel W
Other Authors: Aicher, Toby P , Muema, Daniel M , Carroll, Shaina L , Ordovas-Montanes, Jose , Miao, Vincent N , Tu, Ang A , Ziegler, Carly G K , Nyquist, Sarah K , Wong, Emily B , Ismail, Nasreen , Dong, Mary , Moodley, Amber , Berger, Bonnie , Love, J Christopher , Dong, Krista L , Leslie, Alasdair , Ndhlovu, Zaza M , Ndung'u, Thumbi , Walker, Bruce D , Shalek, Alex K
Format: Electronic Article Electronic Article
Language: English
Subjects:
HIV
RNA
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/32251406
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title: Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection
format: Article
creator:
  • Kazer, Samuel W
  • Aicher, Toby P
  • Muema, Daniel M
  • Carroll, Shaina L
  • Ordovas-Montanes, Jose
  • Miao, Vincent N
  • Tu, Ang A
  • Ziegler, Carly G K
  • Nyquist, Sarah K
  • Wong, Emily B
  • Ismail, Nasreen
  • Dong, Mary
  • Moodley, Amber
  • Berger, Bonnie
  • Love, J Christopher
  • Dong, Krista L
  • Leslie, Alasdair
  • Ndhlovu, Zaza M
  • Ndung'u, Thumbi
  • Walker, Bruce D
  • Shalek, Alex K
subjects:
  • Acute Disease
  • Acute-Phase Reaction - genetics
  • Acute-Phase Reaction - immunology
  • Acute-Phase Reaction - pathology
  • Adolescent
  • Adult
  • Analysis
  • Antiretroviral agents
  • Antiretroviral therapy
  • Blood
  • Cell Communication - genetics
  • Cell Communication - immunology
  • Cell differentiation
  • Cellular immunity
  • Computer applications
  • Diagnosis
  • Differentiation (biology)
  • Female
  • Gene expression
  • Gene Expression Profiling
  • Gene Regulatory Networks - immunology
  • Gene sequencing
  • Genetic aspects
  • HIV
  • HIV infection
  • HIV Infections - genetics
  • HIV Infections - immunology
  • HIV Infections - pathology
  • HIV-1 - genetics
  • HIV-1 - pathogenicity
  • Human immunodeficiency virus
  • Humans
  • Immunity (cell-mediated)
  • Immunity, Cellular - physiology
  • Infections
  • Inflammation
  • Interferon
  • Killer cells
  • Killer Cells, Natural - immunology
  • Killer Cells, Natural - metabolism
  • Leukocytes (mononuclear)
  • Leukocytes, Mononuclear - metabolism
  • Leukocytes, Mononuclear - pathology
  • Longitudinal Studies
  • Lymphocytes
  • Lymphocytes T
  • Major histocompatibility complex
  • Monocytes
  • Natural killer cells
  • Peripheral blood mononuclear cells
  • Ribonucleic acid
  • RNA
  • RNA sequencing
  • Sequence Analysis, RNA - methods
  • Single-Cell Analysis - methods
  • Systems Integration
  • T-Lymphocytes, Cytotoxic - immunology
  • T-Lymphocytes, Cytotoxic - metabolism
  • Usage
  • Viral Load - genetics
  • Viral Load - immunology
  • Young Adult
ispartof: Nature medicine, 2020-04, Vol.26 (4), p.511-518
description: Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease and nominating testable therapeutic targets . Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability . Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection , we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titleIntegrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection
creatorKazer, Samuel W ; Aicher, Toby P ; Muema, Daniel M ; Carroll, Shaina L ; Ordovas-Montanes, Jose ; Miao, Vincent N ; Tu, Ang A ; Ziegler, Carly G K ; Nyquist, Sarah K ; Wong, Emily B ; Ismail, Nasreen ; Dong, Mary ; Moodley, Amber ; Berger, Bonnie ; Love, J Christopher ; Dong, Krista L ; Leslie, Alasdair ; Ndhlovu, Zaza M ; Ndung'u, Thumbi ; Walker, Bruce D ; Shalek, Alex K
creatorcontribKazer, Samuel W ; Aicher, Toby P ; Muema, Daniel M ; Carroll, Shaina L ; Ordovas-Montanes, Jose ; Miao, Vincent N ; Tu, Ang A ; Ziegler, Carly G K ; Nyquist, Sarah K ; Wong, Emily B ; Ismail, Nasreen ; Dong, Mary ; Moodley, Amber ; Berger, Bonnie ; Love, J Christopher ; Dong, Krista L ; Leslie, Alasdair ; Ndhlovu, Zaza M ; Ndung'u, Thumbi ; Walker, Bruce D ; Shalek, Alex K
descriptionCellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease and nominating testable therapeutic targets . Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability . Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection , we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.
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languageeng
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subjectAcute Disease ; Acute-Phase Reaction - genetics ; Acute-Phase Reaction - immunology ; Acute-Phase Reaction - pathology ; Adolescent ; Adult ; Analysis ; Antiretroviral agents ; Antiretroviral therapy ; Blood ; Cell Communication - genetics ; Cell Communication - immunology ; Cell differentiation ; Cellular immunity ; Computer applications ; Diagnosis ; Differentiation (biology) ; Female ; Gene expression ; Gene Expression Profiling ; Gene Regulatory Networks - immunology ; Gene sequencing ; Genetic aspects ; HIV ; HIV infection ; HIV Infections - genetics ; HIV Infections - immunology ; HIV Infections - pathology ; HIV-1 - genetics ; HIV-1 - pathogenicity ; Human immunodeficiency virus ; Humans ; Immunity (cell-mediated) ; Immunity, Cellular - physiology ; Infections ; Inflammation ; Interferon ; Killer cells ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - metabolism ; Leukocytes, Mononuclear - pathology ; Longitudinal Studies ; Lymphocytes ; Lymphocytes T ; Major histocompatibility complex ; Monocytes ; Natural killer cells ; Peripheral blood mononuclear cells ; Ribonucleic acid ; RNA ; RNA sequencing ; Sequence Analysis, RNA - methods ; Single-Cell Analysis - methods ; Systems Integration ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism ; Usage ; Viral Load - genetics ; Viral Load - immunology ; Young Adult
ispartofNature medicine, 2020-04, Vol.26 (4), p.511-518
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descriptionCellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease and nominating testable therapeutic targets . Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability . Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection , we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.
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14Computer applications
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17Female
18Gene expression
19Gene Expression Profiling
20Gene Regulatory Networks - immunology
21Gene sequencing
22Genetic aspects
23HIV
24HIV infection
25HIV Infections - genetics
26HIV Infections - immunology
27HIV Infections - pathology
28HIV-1 - genetics
29HIV-1 - pathogenicity
30Human immunodeficiency virus
31Humans
32Immunity (cell-mediated)
33Immunity, Cellular - physiology
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35Inflammation
36Interferon
37Killer cells
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39Killer Cells, Natural - metabolism
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45Lymphocytes T
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47Monocytes
48Natural killer cells
49Peripheral blood mononuclear cells
50Ribonucleic acid
51RNA
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titleIntegrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection
authorKazer, Samuel W ; Aicher, Toby P ; Muema, Daniel M ; Carroll, Shaina L ; Ordovas-Montanes, Jose ; Miao, Vincent N ; Tu, Ang A ; Ziegler, Carly G K ; Nyquist, Sarah K ; Wong, Emily B ; Ismail, Nasreen ; Dong, Mary ; Moodley, Amber ; Berger, Bonnie ; Love, J Christopher ; Dong, Krista L ; Leslie, Alasdair ; Ndhlovu, Zaza M ; Ndung'u, Thumbi ; Walker, Bruce D ; Shalek, Alex K
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6Analysis
7Antiretroviral agents
8Antiretroviral therapy
9Blood
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12Cell differentiation
13Cellular immunity
14Computer applications
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20Gene Regulatory Networks - immunology
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51RNA
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54Single-Cell Analysis - methods
55Systems Integration
56T-Lymphocytes, Cytotoxic - immunology
57T-Lymphocytes, Cytotoxic - metabolism
58Usage
59Viral Load - genetics
60Viral Load - immunology
61Young Adult
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abstractCellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease and nominating testable therapeutic targets . Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability . Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection , we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.
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