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  1. Article ; Online: SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways.

    Sungnak, Waradon / Huang, Ni / Bécavin, Christophe / Berg, Marijn

    ArXiv

    2020  

    Abstract: The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 coronavirus disease, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ...

    Abstract The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 coronavirus disease, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor,
    Keywords covid19
    Language English
    Publishing date 2020-03-13
    Publishing country United States
    Document type Preprint
    ISSN 2331-8422
    ISSN (online) 2331-8422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Multilayer regulation of CD4 T cell subset differentiation in the era of single cell genomics.

    Sungnak, Waradon / Wang, Chao / Kuchroo, Vijay K

    Advances in immunology

    2019  Volume 141, Page(s) 1–31

    Abstract: CD4 T cells are major immune cell types that mediate effector responses appropriate for diverse incoming threats. These cells have been categorized into different subsets based on how they are induced, expression of specific master transcription factors, ...

    Abstract CD4 T cells are major immune cell types that mediate effector responses appropriate for diverse incoming threats. These cells have been categorized into different subsets based on how they are induced, expression of specific master transcription factors, and the resulting effector cell phenotypes as defined by expression of signature cytokines. However, recent studies assessing the expression of gene modules in single CD4 T cells, rather than expression of one or a few signature genes, have provided a more complex picture in which the canonical model does not fit as cleanly as proposed. Here, we review the concepts of lineage commitment, plasticity and functional heterogeneity in the context of this greater complexity. We then apply our current understanding of CD4 T cell subsets to discuss outstanding questions regarding follicular helper T cells and follicular regulatory T cells with respect to their shared features with other known CD4 T cell subsets.
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Cell Differentiation/immunology ; Cell Lineage/genetics ; Cell Lineage/immunology ; Cytokines/immunology ; Cytokines/metabolism ; Epigenesis, Genetic/immunology ; Gene Regulatory Networks/genetics ; Gene Regulatory Networks/immunology ; Genomics ; Humans ; Mice ; Models, Immunological ; Single-Cell Analysis ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Transcription Factors/immunology
    Chemical Substances Cytokines ; Transcription Factors
    Language English
    Publishing date 2019-01-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80226-8
    ISSN 1557-8445 ; 0065-2776
    ISSN (online) 1557-8445
    ISSN 0065-2776
    DOI 10.1016/bs.ai.2018.12.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Single-cell temporal analysis of natural dengue infection reveals skin-homing lymphocyte expansion one day before defervescence.

    Arora, Jantarika Kumar / Opasawatchai, Anunya / Poonpanichakul, Tiraput / Jiravejchakul, Natnicha / Sungnak, Waradon / Matangkasombut, Oranart / Teichmann, Sarah A / Matangkasombut, Ponpan / Charoensawan, Varodom

    iScience

    2022  Volume 25, Issue 4, Page(s) 104034

    Abstract: Effective clinical management of acute dengue virus (DENV) infection relies on the timing of suitable treatments during the disease progression. We analyzed single-cell transcriptomic profiles of the peripheral blood mononuclear cell samples from two ... ...

    Abstract Effective clinical management of acute dengue virus (DENV) infection relies on the timing of suitable treatments during the disease progression. We analyzed single-cell transcriptomic profiles of the peripheral blood mononuclear cell samples from two DENV patients, collected daily during acute phase and also at convalescence. Key immune cell types demonstrated different dynamic responses over the course of the infection. On the day before defervescence (Day -1), we observed the peak expression of several prominent genes in the adaptive immunological pathways. We also characterized unique effector T cell clusters that expressed skin-homing signature genes at Day -1, whereas upregulation of skin and gut homing genes was also observed in plasma cells and plasmablasts during the febrile period. This work provides an overview of unique molecular dynamics that signify the entry of the critical phase, and the findings could improve the patient management of DENV infection.
    Language English
    Publishing date 2022-03-05
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.104034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Single-cell temporal analysis of natural dengue infection reveals skin-homing lymphocyte expansion one day before defervescence

    Jantarika Kumar Arora / Anunya Opasawatchai / Tiraput Poonpanichakul / Natnicha Jiravejchakul / Waradon Sungnak / Oranart Matangkasombut / Sarah A. Teichmann / Ponpan Matangkasombut / Varodom Charoensawan / Anavaj Sakuntabhai / Pratap Singhasivanon / Swangjit Suraamornkul / Tawatchai Yingtaweesak / Khajohnpong Manopwisedjaroen / Nada Pitabut

    iScience, Vol 25, Iss 4, Pp 104034- (2022)

    2022  

    Abstract: Summary: Effective clinical management of acute dengue virus (DENV) infection relies on the timing of suitable treatments during the disease progression. We analyzed single-cell transcriptomic profiles of the peripheral blood mononuclear cell samples ... ...

    Abstract Summary: Effective clinical management of acute dengue virus (DENV) infection relies on the timing of suitable treatments during the disease progression. We analyzed single-cell transcriptomic profiles of the peripheral blood mononuclear cell samples from two DENV patients, collected daily during acute phase and also at convalescence. Key immune cell types demonstrated different dynamic responses over the course of the infection. On the day before defervescence (Day −1), we observed the peak expression of several prominent genes in the adaptive immunological pathways. We also characterized unique effector T cell clusters that expressed skin-homing signature genes at Day −1, whereas upregulation of skin and gut homing genes was also observed in plasma cells and plasmablasts during the febrile period. This work provides an overview of unique molecular dynamics that signify the entry of the critical phase, and the findings could improve the patient management of DENV infection.
    Keywords Single-cell Omics ; Systems biology ; Immunology ; Science ; Q
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Book ; Online: SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways

    Sungnak, Waradon / Huang, Ni / Bécavin, Christophe / Berg, Marijn / Network, HCA Lung Biological

    2020  

    Abstract: The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 coronavirus disease, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ACE2, as well as the viral S protein priming ...

    Abstract The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 coronavirus disease, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ACE2, as well as the viral S protein priming protease TMPRSS2 thought to govern viral entry in single-cell RNA-sequencing (scRNA-seq) datasets from healthy individuals generated by the Human Cell Atlas consortium. We found that ACE2, as well as the protease TMPRSS2, are differentially expressed in respiratory and gut epithelial cells. In-depth analysis of epithelial cells in the respiratory tree reveals that nasal epithelial cells, specifically goblet/secretory cells and ciliated cells, display the highest ACE2 expression of all the epithelial cells analyzed. The skewed expression of viral receptors/entry-associated proteins towards the upper airway may be correlated with enhanced transmissivity. Finally, we showed that many of the top genes associated with ACE2 airway epithelial expression are innate immune-associated, antiviral genes, highly enriched in the nasal epithelial cells. This association with immune pathways might have clinical implications for the course of infection and viral pathology, and highlights the specific significance of nasal epithelia in viral infection. Our findings underscore the importance of the availability of the Human Cell Atlas as a reference dataset. In this instance, analysis of the compendium of data points to a particularly relevant role for nasal goblet and ciliated cells as early viral targets and potential reservoirs of SARS-CoV-2 infection. This, in turn, serves as a biological framework for dissecting viral transmission and developing clinical strategies for prevention and therapy.
    Keywords Quantitative Biology - Cell Behavior ; covid19
    Subject code 570
    Publishing date 2020-03-13
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes.

    Sungnak, Waradon / Huang, Ni / Bécavin, Christophe / Berg, Marijn / Queen, Rachel / Litvinukova, Monika / Talavera-López, Carlos / Maatz, Henrike / Reichart, Daniel / Sampaziotis, Fotios / Worlock, Kaylee B / Yoshida, Masahiro / Barnes, Josephine L

    Nature medicine

    2020  Volume 26, Issue 5, Page(s) 681–687

    Abstract: We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and ...

    Abstract We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells' potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
    Keywords covid19
    Language English
    Publishing date 2020-04-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-020-0868-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes

    Sungnak, Waradon / Huang, Ni / Bécavin, Christophe / Berg, Marijn / Queen, Rachel / Litvinukova, Monika / Talavera-López, Carlos / Maatz, Henrike / Reichart, Daniel / Sampaziotis, Fotios / Worlock, Kaylee B. / Yoshida, Masahiro / Barnes, Josephine L.

    Nature Medicine

    2020  Volume 26, Issue 5, Page(s) 681–687

    Keywords General Biochemistry, Genetics and Molecular Biology ; General Medicine ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-020-0868-6
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: T Follicular Regulatory Cell-Derived Fibrinogen-like Protein 2 Regulates Production of Autoantibodies and Induction of Systemic Autoimmunity.

    Sungnak, Waradon / Wagner, Allon / Kowalczyk, Monika S / Bod, Lloyd / Kye, Yoon-Chul / Sage, Peter T / Sharpe, Arlene H / Sobel, Raymond A / Quintana, Francisco J / Rozenblatt-Rosen, Orit / Regev, Aviv / Wang, Chao / Yosef, Nir / Kuchroo, Vijay K

    Journal of immunology (Baltimore, Md. : 1950)

    2020  Volume 205, Issue 12, Page(s) 3247–3262

    Abstract: T follicular regulatory (TFR) cells limit Ab responses, but the underlying mechanisms remain largely unknown. In this study, we identify Fgl2 as a soluble TFR cell effector molecule through single-cell gene expression profiling. Highly expressed by TFR ... ...

    Abstract T follicular regulatory (TFR) cells limit Ab responses, but the underlying mechanisms remain largely unknown. In this study, we identify Fgl2 as a soluble TFR cell effector molecule through single-cell gene expression profiling. Highly expressed by TFR cells, Fgl2 directly binds to B cells, especially light-zone germinal center B cells, as well as to T follicular helper (TFH) cells, and directly regulates B cells and TFH in a context-dependent and type 2 Ab isotype-specific manner. In TFH cells, Fgl2 induces the expression of Prdm1 and a panel of checkpoint molecules, including PD1, TIM3, LAG3, and TIGIT, resulting in TFH cell dysfunction. Mice deficient in Fgl2 had dysregulated Ab responses at steady-state and upon immunization. In addition, loss of Fgl2 results in expansion of autoreactive B cells upon immunization. Consistent with this observation, aged Fgl2
    MeSH term(s) Animals ; Antibody Formation ; Antigens, CD/genetics ; Antigens, CD/immunology ; Autoantibodies/immunology ; Autoimmune Diseases/genetics ; Autoimmune Diseases/immunology ; B-Lymphocytes/immunology ; Fibrinogen/genetics ; Fibrinogen/immunology ; Hepatitis A Virus Cellular Receptor 2/genetics ; Hepatitis A Virus Cellular Receptor 2/immunology ; Mice ; Mice, Knockout ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/immunology ; Receptors, Immunologic/genetics ; Receptors, Immunologic/immunology ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances Antigens, CD ; Autoantibodies ; CD223 antigen ; Fgl2 protein, mouse ; Havcr2 protein, mouse ; Hepatitis A Virus Cellular Receptor 2 ; Pdcd1 protein, mouse ; Programmed Cell Death 1 Receptor ; Receptors, Immunologic ; T cell Ig and ITIM domain protein, mouse ; Fibrinogen (9001-32-5)
    Language English
    Publishing date 2020-11-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2000748
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes

    Barbry, Pascal / Sungnak, Waradon / Huang, Ni / Bécavin, Christophe / Berg, Marijn / Queen, Rachel / Litvinukova, Monika / Talavera-López, Carlos / Maatz, Henrike / Reichart, Daniel / Sampaziotis, Fotios / Worlock, Kaylee / Yoshida, Masahiro / Barnes, Josephine

    ISSN: 1078-8956 ; EISSN: 1744-7933 ; Nature Medicine ; https://hal.archives-ouvertes.fr/hal-02992326 ; Nature Medicine, Nature Publishing Group, 2020, 26 (5), pp.681-687. ⟨10.1038/s41591-020-0868-6⟩

    2020  

    Abstract: International ... ...

    Abstract International audience
    Keywords [SDV]Life Sciences [q-bio] ; covid19
    Language English
    Publisher HAL CCSD
    Publishing country fr
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes

    Barbry, Pascal / Sungnak, Waradon / Huang, Ni / Bécavin, Christophe / Berg, Marijn / Queen, Rachel / Litvinukova, Monika / Talavera-López, Carlos / Maatz, Henrike / Reichart, Daniel / Sampaziotis, Fotios / Worlock, Kaylee / Yoshida, Masahiro / Barnes, Josephine

    ISSN: 1078-8956 ; EISSN: 1744-7933 ; Nature Medicine ; https://hal.archives-ouvertes.fr/hal-02992326 ; Nature Medicine, Nature Publishing Group, 2020, 26 (5), pp.681-687. ⟨10.1038/s41591-020-0868-6⟩

    2020  

    Abstract: International ... ...

    Abstract International audience
    Keywords [SDV]Life Sciences [q-bio] ; covid19
    Language English
    Publisher HAL CCSD
    Publishing country fr
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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