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  1. Article ; Online: Single-cell atlas of early chick development reveals gradual segregation of neural crest lineage from the neural plate border during neurulation.

    Williams, Ruth M / Lukoseviciute, Martyna / Sauka-Spengler, Tatjana / Bronner, Marianne E

    eLife

    2022  Volume 11

    Abstract: The epiblast of vertebrate embryos is comprised of neural and non-neural ectoderm, with the border territory at their intersection harboring neural crest and cranial placode progenitors. Here, we a generate single-cell atlas of the developing chick ... ...

    Abstract The epiblast of vertebrate embryos is comprised of neural and non-neural ectoderm, with the border territory at their intersection harboring neural crest and cranial placode progenitors. Here, we a generate single-cell atlas of the developing chick epiblast from late gastrulation through early neurulation stages to define transcriptional changes in the emerging 'neural plate border' as well as other regions of the epiblast. Focusing on the border territory, the results reveal gradual establishment of heterogeneous neural plate border signatures, including novel genes that we validate by fluorescent in situ hybridization. Developmental trajectory analysis infers that segregation of neural plate border lineages only commences at early neurulation, rather than at gastrulation as previously predicted. We find that cells expressing the prospective neural crest marker
    MeSH term(s) Animals ; Chick Embryo/cytology ; Chickens/physiology ; Gene Expression Regulation, Developmental ; Germ Layers/physiology ; In Situ Hybridization, Fluorescence ; Neural Crest/embryology ; Neural Plate/embryology ; Neurulation/physiology ; PAX7 Transcription Factor/analysis
    Chemical Substances PAX7 Transcription Factor
    Language English
    Publishing date 2022-01-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.74464
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Multi-layered transcriptional control of cranial neural crest development.

    Candido-Ferreira, Ivan L / Lukoseviciute, Martyna / Sauka-Spengler, Tatjana

    Seminars in cell & developmental biology

    2022  Volume 138, Page(s) 1–14

    Abstract: The neural crest (NC) is an emblematic population of embryonic stem-like cells with remarkable migratory ability. These distinctive attributes have inspired the curiosity of developmental biologists for over 150 years, however only recently the ... ...

    Abstract The neural crest (NC) is an emblematic population of embryonic stem-like cells with remarkable migratory ability. These distinctive attributes have inspired the curiosity of developmental biologists for over 150 years, however only recently the regulatory mechanisms controlling the complex features of the NC have started to become elucidated at genomic scales. Regulatory control of NC development is achieved through combinatorial transcription factor binding and recruitment of associated transcriptional complexes to distal cis-regulatory elements. Together, they regulate when, where and to what extent transcriptional programmes are actively deployed, ultimately shaping ontogenetic processes. Here, we discuss how transcriptional networks control NC ontogeny, with a special emphasis on the molecular mechanisms underlying specification of the cephalic NC. We also cover emerging properties of transcriptional regulation revealed in diverse developmental systems, such as the role of three-dimensional conformation of chromatin, and how they are involved in the regulation of NC ontogeny. Finally, we highlight how advances in deciphering the NC transcriptional network have afforded new insights into the molecular basis of human diseases.
    MeSH term(s) Humans ; Neural Crest/metabolism ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Neurogenesis ; Embryonic Stem Cells
    Language English
    Publishing date 2022-08-06
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1312473-0
    ISSN 1096-3634 ; 1084-9521
    ISSN (online) 1096-3634
    ISSN 1084-9521
    DOI 10.1016/j.semcdb.2022.07.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Multi-layered transcriptional control of cranial neural crest development

    Candido-Ferreira, Ivan L. / Lukoseviciute, Martyna / Sauka-Spengler, Tatjana

    Seminars in cell & developmental biology. 2022 July 23,

    2022  

    Abstract: The neural crest (NC) is an emblematic population of embryonic stem-like cells with remarkable migratory ability. These distinctive attributes have inspired the curiosity of developmental biologists for over 150 years, however only recently the ... ...

    Abstract The neural crest (NC) is an emblematic population of embryonic stem-like cells with remarkable migratory ability. These distinctive attributes have inspired the curiosity of developmental biologists for over 150 years, however only recently the regulatory mechanisms controlling the complex features of the NC have started to become elucidated at genomic scales. Regulatory control of NC development is achieved through combinatorial transcription factor binding and recruitment of associated transcriptional complexes to distal cis-regulatory elements. Together, they regulate when, where and to what extent transcriptional programmes are actively deployed, ultimately shaping ontogenetic processes. Here, we discuss how transcriptional networks control NC ontogeny, with a special emphasis on the molecular mechanisms underlying specification of the cephalic NC. We also cover emerging properties of transcriptional regulation revealed in diverse developmental systems, such as the role of three-dimensional conformation of chromatin, and how they are involved in the regulation of NC ontogeny. Finally, we highlight how advances in deciphering the NC transcriptional network have afforded new insights into the molecular basis of human diseases.
    Keywords chromatin ; genomics ; humans ; migratory behavior ; neural crest ; ontogeny ; transcription (genetics) ; transcription factors
    Language English
    Dates of publication 2022-0723
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 1312473-0
    ISSN 1096-3634 ; 1084-9521
    ISSN (online) 1096-3634
    ISSN 1084-9521
    DOI 10.1016/j.semcdb.2022.07.010
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Tissue-Specific

    Lukoseviciute, Martyna / Ling, Irving T C / Senanayake, Upeka / Candido-Ferreira, Ivan / Taylor, Gunes / Williams, Ruth M / Sauka-Spengler, Tatjana

    STAR protocols

    2020  Volume 1, Issue 2, Page(s) 100066

    Abstract: Chromatin immunoprecipitation with sequencing (ChIP-seq) has been instrumental in understanding transcription factor (TF) binding during gene regulation. ChIP-seq requires specific antibodies against desired TFs, which are not available for numerous ... ...

    Abstract Chromatin immunoprecipitation with sequencing (ChIP-seq) has been instrumental in understanding transcription factor (TF) binding during gene regulation. ChIP-seq requires specific antibodies against desired TFs, which are not available for numerous species. Here, we describe a tissue-specific biotin ChIP-seq protocol for zebrafish and chicken embryos which utilizes AVI tagging of TFs, permitting their biotinylation by a co-expressed nuclear biotin ligase. Subsequently, biotinylated factors can be precipitated with streptavidin beads, enabling the user to construct TF genome-wide binding landscapes like conventional ChIP-seq methods. For complete details on the use and execution of this protocol, please see Lukoseviciute et al. (2018) and Ling and Sauka-Spengler (2019).
    MeSH term(s) Animals ; Biotin/chemistry ; Biotin/metabolism ; Cells, Cultured ; Chickens/genetics ; Chromatin Immunoprecipitation/methods ; Organ Specificity/physiology ; Sequence Analysis, DNA/methods ; Streptavidin/chemistry ; Streptavidin/metabolism ; Transcription Factors/chemistry ; Transcription Factors/metabolism ; Zebrafish/genetics
    Chemical Substances Transcription Factors ; Biotin (6SO6U10H04) ; Streptavidin (9013-20-1)
    Language English
    Publishing date 2020-07-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2020.100066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Nanoscale dynamics of cholesterol in the cell membrane.

    Pinkwart, Kerstin / Schneider, Falk / Lukoseviciute, Martyna / Sauka-Spengler, Tatjana / Lyman, Edward / Eggeling, Christian / Sezgin, Erdinc

    The Journal of biological chemistry

    2019  Volume 294, Issue 34, Page(s) 12599–12609

    Abstract: Cholesterol constitutes ∼30-40% of the mammalian plasma membrane, a larger fraction than of any other single component. It is a major player in numerous signaling processes as well as in shaping molecular membrane architecture. However, our knowledge of ... ...

    Abstract Cholesterol constitutes ∼30-40% of the mammalian plasma membrane, a larger fraction than of any other single component. It is a major player in numerous signaling processes as well as in shaping molecular membrane architecture. However, our knowledge of the dynamics of cholesterol in the plasma membrane is limited, restricting our understanding of the mechanisms regulating its involvement in cell signaling. Here, we applied advanced fluorescence imaging and spectroscopy approaches on
    MeSH term(s) Animals ; CHO Cells ; Cell Membrane/chemistry ; Cell Membrane/metabolism ; Cells, Cultured ; Cholesterol/analysis ; Cholesterol/metabolism ; Cricetulus ; Diffusion ; Female ; Male ; Molecular Dynamics Simulation ; Monte Carlo Method ; Nanotechnology ; Spectrometry, Fluorescence ; Zebrafish
    Chemical Substances Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2019-07-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA119.009683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: From Pioneer to Repressor: Bimodal foxd3 Activity Dynamically Remodels Neural Crest Regulatory Landscape In Vivo.

    Lukoseviciute, Martyna / Gavriouchkina, Daria / Williams, Ruth M / Hochgreb-Hagele, Tatiana / Senanayake, Upeka / Chong-Morrison, Vanessa / Thongjuea, Supat / Repapi, Emmanouela / Mead, Adam / Sauka-Spengler, Tatjana

    Developmental cell

    2018  Volume 47, Issue 5, Page(s) 608–628.e6

    Abstract: The neural crest (NC) is a transient embryonic stem cell-like population characterized by its multipotency and broad developmental potential. Here, we perform NC-specific transcriptional and epigenomic profiling of foxd3-mutant cells in vivo to define ... ...

    Abstract The neural crest (NC) is a transient embryonic stem cell-like population characterized by its multipotency and broad developmental potential. Here, we perform NC-specific transcriptional and epigenomic profiling of foxd3-mutant cells in vivo to define the gene regulatory circuits controlling NC specification. Together with global binding analysis obtained by foxd3 biotin-ChIP and single cell profiles of foxd3-expressing premigratory NC, our analysis shows that, during early steps of NC formation, foxd3 acts globally as a pioneer factor to prime the onset of genes regulating NC specification and migration by re-arranging the chromatin landscape, opening cis-regulatory elements and reshuffling nucleosomes. Strikingly, foxd3 then gradually switches from an activator to its well-described role as a transcriptional repressor and potentially uses differential partners for each role. Taken together, these results demonstrate that foxd3 acts bimodally in the neural crest as a switch from "permissive" to "repressive" nucleosome and chromatin organization to maintain multipotency and define cell fates.
    MeSH term(s) Animals ; Chromatin Assembly and Disassembly ; Enhancer Elements, Genetic ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Gene Expression Regulation, Developmental ; Neural Crest/embryology ; Neural Crest/metabolism ; Zebrafish ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
    Chemical Substances Forkhead Transcription Factors ; Zebrafish Proteins ; foxd3 protein, zebrafish
    Language English
    Publishing date 2018-11-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2018.11.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

    Ahern, David J. / Ai, Zhichao / Ainsworth, Mark / Allan, Chris / Allcock, Alice / Angus, Brian / Ansari, M. Azim / Arancibia-Cárcamo, Carolina V. / Aschenbrenner, Dominik / Attar, Moustafa / Baillie, J. Kenneth / Barnes, Eleanor / Bashford-Rogers, Rachael / Bashyal, Archana / Beer, Sally / Berridge, Georgina / Beveridge, Amy / Bibi, Sagida / Bicanic, Tihana /
    Blackwell, Luke / Bowness, Paul / Brent, Andrew / Brown, Andrew / Broxholme, John / Buck, David / Burnham, Katie L. / Byrne, Helen / Camara, Susana / Candido Ferreira, Ivan / Charles, Philip / Chen, Wentao / Chen, Yi-Ling / Chong, Amanda / Clutterbuck, Elizabeth A. / Coles, Mark / Conlon, Christopher P. / Cornall, Richard / Cribbs, Adam P. / Curion, Fabiola / Davenport, Emma E. / Davidson, Neil / Davis, Simon / Dendrou, Calliope A. / Dequaire, Julie / Dib, Lea / Docker, James / Dold, Christina / Dong, Tao / Downes, Damien / Drakesmith, Hal / Dunachie, Susanna J. / Duncan, David A. / Eijsbouts, Chris / Esnouf, Robert / Espinosa, Alexis / Etherington, Rachel / Fairfax, Benjamin / Fairhead, Rory / Fang, Hai / Fassih, Shayan / Felle, Sally / Fernandez Mendoza, Maria / Ferreira, Ricardo / Fischer, Roman / Foord, Thomas / Forrow, Aden / Frater, John / Fries, Anastasia / Gallardo Sanchez, Veronica / Garner, Lucy C. / Geeves, Clementine / Georgiou, Dominique / Godfrey, Leila / Golubchik, Tanya / Gomez Vazquez, Maria / Green, Angie / Harper, Hong / Harrington, Heather A. / Heilig, Raphael / Hester, Svenja / Hill, Jennifer / Hinds, Charles / Hird, Clare / Ho, Ling-Pei / Hoekzema, Renee / Hollis, Benjamin / Hughes, Jim / Hutton, Paula / Jackson-Wood, Matthew A. / Jainarayanan, Ashwin / James-Bott, Anna / Jansen, Kathrin / Jeffery, Katie / Jones, Elizabeth / Jostins, Luke / Kerr, Georgina / Kim, David / Klenerman, Paul / Knight, Julian C. / Kumar, Vinod / Kumar Sharma, Piyush / Kurupati, Prathiba / Kwok, Andrew / Lee, Angela / Linder, Aline / Lockett, Teresa / Lonie, Lorne / Lopopolo, Maria / Lukoseviciute, Martyna / Luo, Jian / Marinou, Spyridoula / Marsden, Brian / Martinez, Jose / Matthews, Philippa C. / Mazurczyk, Michalina / McGowan, Simon / McKechnie, Stuart / Mead, Adam / Mentzer, Alexander J. / Mi, Yuxin / Monaco, Claudia / Montadon, Ruddy / Napolitani, Giorgio / Nassiri, Isar / Novak, Alex / O'Brien, Darragh P. / O'Connor, Daniel / O'Donnell, Denise / Ogg, Graham / Overend, Lauren / Park, Inhye / Pavord, Ian / Peng, Yanchun / Penkava, Frank / Pereira Pinho, Mariana / Perez, Elena / Pollard, Andrew J. / Powrie, Fiona / Psaila, Bethan / Quan, T. Phuong / Repapi, Emmanouela / Revale, Santiago / Silva-Reyes, Laura / Richard, Jean-Baptiste / Rich-Griffin, Charlotte / Ritter, Thomas / Rollier, Christine S. / Rowland, Matthew / Ruehle, Fabian / Salio, Mariolina / Sansom, Stephen Nicholas / Sanches Peres, Raphael / Santos Delgado, Alberto / Sauka-Spengler, Tatjana / Schwessinger, Ron / Scozzafava, Giuseppe / Screaton, Gavin / Seigal, Anna / Semple, Malcolm G. / Sergeant, Martin / Simoglou Karali, Christina / Sims, David / Skelly, Donal / Slawinski, Hubert / Sobrinodiaz, Alberto / Sousos, Nikolaos / Stafford, Lizzie / Stockdale, Lisa / Strickland, Marie / Sumray, Otto / Sun, Bo / Taylor, Chelsea / Taylor, Stephen / Taylor, Adan / Thongjuea, Supat / Thraves, Hannah / Todd, John A. / Tomic, Adriana / Tong, Orion / Trebes, Amy / Trzupek, Dominik / Tucci, Felicia Anna / Turtle, Lance / Udalova, Irina / Uhlig, Holm / van Grinsven, Erinke / Vendrell, Iolanda / Verheul, Marije / Voda, Alexandru / Wang, Guanlin / Wang, Lihui / Wang, Dapeng / Watkinson, Peter / Watson, Robert / Weinberger, Michael / Whalley, Justin / Witty, Lorna / Wray, Katherine / Xue, Luzheng / Yeung, Hing Yuen / Yin, Zixi / Young, Rebecca K. / Youngs, Jonathan / Zhang, Ping / Zurke, Yasemin-Xiomara

    Cell. 2022 Mar. 03, v. 185, no. 5

    2022  

    Abstract: Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated ... ...

    Institution COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium
    Abstract Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19.
    Keywords COVID-19 infection ; biomarkers ; clinical trials ; coagulation ; disease severity ; drug development ; influenza ; metabolism ; patients ; precision medicine ; proteome
    Language English
    Dates of publication 2022-0303
    Size p. 916-938.e58.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2022.01.012
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

    The COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium / Ahern, David J / Ai, Zhichao / Ainsworth, Mark / Allan, Chris / Allcock, Alice / Ansari, Azim / Arancibia-Carcamo, Carolina V / Aschenbrenner, Dominik / Attar, Moustafa / Baillie, J. Kenneth / Barnes, Eleanor / Bashford-Rogers, Rachael / Bashyal, Archana / Beer, Sally / Berridge, Georgina / Beveridge, Amy / Bibi, Sagida / Bicanic, Tihana /
    Blackwell, Luke / Bowness, Paul / Brent, Andrew / Brown, Andrew / Broxholme, John / Buck, David / Burnham, Katie L / Byrne, Helen / Camara, Susana / Candido Ferreira, Ivan / Charles, Philip / Chen, Wentao / Chen, Yi-Ling / Chong, Amanda / Clutterbuck, Elizabeth / Coles, Mark / Conlon, Christopher P / Cornall, Richard / Cribbs, Adam P / Curion, Fabiola / Davenport, Emma E / Davidson, Neil / Davis, Simon / Dendrou, Calliope / Dequaire, Julie / Dib, Lea / Docker, James / Dold, Christina / Dong, Tao / Downes, Damien / Drakesmith, Alexander / Dunachie, Susanna J / Duncan, David A / Eijsbouts, Chris / Esnouf, Robert / Espinosa, Alexis / Etherington, Rachel / Fairfax, Benjamin / Fairhead, Rory / Fang, Hai / Fassih, Shayan / Felle, Sally / Fernandez Mendoza, Maria / Ferreira, Ricardo / Fischer, Roman / Foord, Thomas / Forrow, Aden / Frater, John / Fries, Anastasia / Gallardo Sanchez, Veronica / Garner, Lucy / Geeves, Clementine / Georgiou, Dominique / Godfrey, Leila / Golubchik, Tanya / Gomez Vazquez, Maria / Green, Angie / Harper, Hong / Harrington, Heather A / Heilig, Raphael / Hester, Svenja / Hill, Jennifer / Hinds, Charles / Hird, Clare / Ho, Ling-Pei / Hoekzema, Renee / Hollis, Benjamin / Hughes, Jim / Hutton, Paula / Jackson, Matthew / Jainarayanan, Ashwin / James-Bott, Anna / Jansen, Kathrin / Jeffery, Katie / Jones, Elizabeth / Jostins, Luke / Kerr, Georgina / Kim, David / Klenerman, Paul / Knight, Julian C / Kumar, Vinod / Kumar Sharma, Piyush / Kurupati, Prathiba / Kwok, Andrew / Lee, Angela / Linder, Aline / Lockett, Teresa / Lonie, Lorne / Lopopolo, Maria / Lukoseviciute, Martyna / Luo, Jian / Marinou, Spyridoula / Marsden, Brian / Martinez, Jose / Matthews, Philippa / Mazurczyk, Michalina / McGowan, Simon / McKechnie, Stuart / Mead, Adam / Mentzer, Alexander J / Mi, Yuxin / Monaco, Claudia / Montadon, Ruddy / Napolitani, Giorgio / Nassiri, Isar / Novak, Alex / O'Brien, Darragh / O'Connor, Daniel / O'Donnell, Denise / Ogg, Graham / Overend, Lauren / Park, Inhye / Pavord, Ian / Peng, Yanchun / Penkava, Frank / Pereira Pinho, Mariana / Perez, Elena / Pollard, Andrew J / Powrie, Fiona / Psaila, Bethan / Quan, T. Phuong / Repapi, Emmanouela / Revale, Santiago / Silva-Reyes, Laura / Richard, Jean-Baptiste / Rich-Griffin, Charlotte / Ritter, Thomas / Rollier, Christine S / Rowland, Matthew / Ruehle, Fabian / Salio, Mariolina / Sansom, Stephen N / Santos Delgado, Alberto / Sauka-Spengler, Tatjana / Schwessinger, Ron / Scozzafava, Giuseppe / Screaton, Gavin / Seigal, Anna / Semple, Malcolm G / Sergeant, Martin / Simoglou Karali, Christina / Sims, David / Skelly, Donal / Slawinski, Hubert / Sobrinodiaz, Alberto / Sousos, Nikolaos / Stafford, Lizzie / Stockdale, Lisa / Strickland, Marie / Sumray, Otto / Sun, Bo / Taylor, Chelsea / Taylor, Stephen / Taylor, Adan / Thongjuea, Supat / Thraves, Hannah / Todd, John A / Tomic, Adriana / Tong, Orion / Trebes, Amy / Trzupek, Dominik / Tucci, Felicia A / Turtle, Lance / Udalova, Irina / Uhlig, Holm / van Grinsven, Erinke / Vendrell, Iolanda / Verheul, Marije / Voda, Alexandru / Wang, Guanlin / Wang, Lihui / Wang, Dapeng / Watkinson, Peter / Watson, Robert / Weinberger, Michael / Whalley, Justin / Witty, Lorna / Wray, Katherine / Xue, Luzheng / Yeung, Hing Yuen / Yin, Zixi / Young, Rebecca K / Youngs, Jonathan / Zhang, Ping / Zurke, Yasemin-Xiomara

    medRxiv

    Abstract: Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying ... ...

    Abstract Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.
    Keywords covid19
    Language English
    Publishing date 2021-05-11
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.05.11.21256877
    Database COVID19

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