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  1. Article ; Online: Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology.

    Wood, Jack I / Wong, Eugenia / Joghee, Ridwaan / Balbaa, Aya / Vitanova, Karina S / Stringer, Katie M / Vanshoiack, Alison / Phelan, Stefan-Laural J / Launchbury, Francesca / Desai, Sneha / Tripathi, Takshashila / Hanrieder, Jörg / Cummings, Damian M / Hardy, John / Edwards, Frances A

    Cell reports

    2022  Volume 41, Issue 8, Page(s) 111686

    Abstract: Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer's mouse model with late plaque development. In 18-month-old ... ...

    Abstract Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer's mouse model with late plaque development. In 18-month-old APP
    MeSH term(s) Animals ; Mice ; Microglia/metabolism ; Alzheimer Disease/metabolism ; Plaque, Amyloid/metabolism ; Amyloidosis ; Amyloidogenic Proteins/metabolism ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism
    Chemical Substances Amyloidogenic Proteins ; Trem2 protein, mouse ; Membrane Glycoproteins ; Receptors, Immunologic
    Language English
    Publishing date 2022-11-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2022.111686
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension.

    Yu, Yen-Rei A / Malakhau, Yuryi / Yu, Chen-Hsin A / Phelan, Stefan-Laural J / Cumming, R Ian / Kan, Matthew J / Mao, Lan / Rajagopal, Sudarshan / Piantadosi, Claude A / Gunn, Michael D

    Journal of immunology (Baltimore, Md. : 1950)

    2020  Volume 204, Issue 6, Page(s) 1474–1485

    Abstract: An increasing body of evidence suggests that bone marrow-derived myeloid cells play a critical role in the pathophysiology of pulmonary hypertension (PH). However, the true requirement for myeloid cells in PH development has not been demonstrated, and a ... ...

    Abstract An increasing body of evidence suggests that bone marrow-derived myeloid cells play a critical role in the pathophysiology of pulmonary hypertension (PH). However, the true requirement for myeloid cells in PH development has not been demonstrated, and a specific disease-promoting myeloid cell population has not been identified. Using bone marrow chimeras, lineage labeling, and proliferation studies, we determined that, in murine hypoxia-induced PH, Ly6C
    MeSH term(s) Animals ; Antigens, Ly/metabolism ; Bone Marrow Transplantation ; Cell Differentiation/immunology ; Disease Models, Animal ; Humans ; Hypertension, Pulmonary/immunology ; Hypertension, Pulmonary/pathology ; Hypertension, Pulmonary/surgery ; Hypoxia/complications ; Hypoxia/immunology ; Hypoxia/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Lung/blood supply ; Lung/immunology ; Lung/pathology ; Lung Transplantation ; Macrophages, Alveolar/immunology ; Macrophages, Alveolar/metabolism ; Male ; Mice ; Mice, Transgenic ; Monocytes/immunology ; Monocytes/metabolism ; Pulmonary Artery/cytology ; Pulmonary Artery/immunology ; Pulmonary Artery/pathology ; Transplantation Chimera/immunology ; Vascular Remodeling/genetics ; Vascular Remodeling/immunology
    Chemical Substances Antigens, Ly ; Hif1a protein, mouse ; Hypoxia-Inducible Factor 1, alpha Subunit ; Ly-6C antigen, mouse
    Language English
    Publishing date 2020-01-29
    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.1900239
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies.

    Dinnon, Kenneth H / Leist, Sarah R / Okuda, Kenichi / Dang, Hong / Fritch, Ethan J / Gully, Kendra L / De la Cruz, Gabriela / Evangelista, Mia D / Asakura, Takanori / Gilmore, Rodney C / Hawkins, Padraig / Nakano, Satoko / West, Ande / Schäfer, Alexandra / Gralinski, Lisa E / Everman, Jamie L / Sajuthi, Satria P / Zweigart, Mark R / Dong, Stephanie /
    McBride, Jennifer / Cooley, Michelle R / Hines, Jesse B / Love, Miriya K / Groshong, Steve D / VanSchoiack, Alison / Phelan, Stefan J / Liang, Yan / Hether, Tyler / Leon, Michael / Zumwalt, Ross E / Barton, Lisa M / Duval, Eric J / Mukhopadhyay, Sanjay / Stroberg, Edana / Borczuk, Alain / Thorne, Leigh B / Sakthivel, Muthu K / Lee, Yueh Z / Hagood, James S / Mock, Jason R / Seibold, Max A / O'Neal, Wanda K / Montgomery, Stephanie A / Boucher, Richard C / Baric, Ralph S

    bioRxiv : the preprint server for biology

    2022  

    Abstract: COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress ... ...

    Abstract COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery. At 15-120 days post-virus clearance, histologic evaluation identified subpleural lesions containing collagen, proliferative fibroblasts, and chronic inflammation with tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal upregulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
    Language English
    Publishing date 2022-02-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.02.15.480515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice.

    Dinnon, Kenneth H / Leist, Sarah R / Okuda, Kenichi / Dang, Hong / Fritch, Ethan J / Gully, Kendra L / De la Cruz, Gabriela / Evangelista, Mia D / Asakura, Takanori / Gilmore, Rodney C / Hawkins, Padraig / Nakano, Satoko / West, Ande / Schäfer, Alexandra / Gralinski, Lisa E / Everman, Jamie L / Sajuthi, Satria P / Zweigart, Mark R / Dong, Stephanie /
    McBride, Jennifer / Cooley, Michelle R / Hines, Jesse B / Love, Miriya K / Groshong, Steve D / VanSchoiack, Alison / Phelan, Stefan J / Liang, Yan / Hether, Tyler / Leon, Michael / Zumwalt, Ross E / Barton, Lisa M / Duval, Eric J / Mukhopadhyay, Sanjay / Stroberg, Edana / Borczuk, Alain / Thorne, Leigh B / Sakthivel, Muthu K / Lee, Yueh Z / Hagood, James S / Mock, Jason R / Seibold, Max A / O'Neal, Wanda K / Montgomery, Stephanie A / Boucher, Richard C / Baric, Ralph S

    Science translational medicine

    2022  Volume 14, Issue 664, Page(s) eabo5070

    Abstract: A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from ... ...

    Abstract A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an acute respiratory distress syndrome in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days after virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of profibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early antifibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
    MeSH term(s) Animals ; Antiviral Agents ; COVID-19/complications ; Fibrosis ; Humans ; Lung/pathology ; Mice ; SARS-CoV-2
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2022-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abo5070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

    Pita-Juarez, Yered / Karagkouni, Dimitra / Kalavros, Nikolaos / Melms, Johannes C / Niezen, Sebastian / Delorey, Toni M / Essene, Adam L / Brook, Olga R / Pant, Deepti / Skelton-Badlani, Disha / Naderi, Pourya / Huang, Pinzhu / Pan, Liuliu / Hether, Tyler / Andrews, Tallulah S / Ziegler, Carly G K / Reeves, Jason / Myloserdnyy, Andriy / Chen, Rachel /
    Nam, Andy / Phelan, Stefan / Liang, Yan / Amin, Amit Dipak / Biermann, Jana / Hibshoosh, Hanina / Veregge, Molly / Kramer, Zachary / Jacobs, Christopher / Yalcin, Yusuf / Phillips, Devan / Slyper, Michal / Subramanian, Ayshwarya / Ashenberg, Orr / Bloom-Ackermann, Zohar / Tran, Victoria M / Gomez, James / Sturm, Alexander / Zhang, Shuting / Fleming, Stephen J / Warren, Sarah / Beechem, Joseph / Hung, Deborah / Babadi, Mehrtash / Padera, Robert F / MacParland, Sonya A / Bader, Gary D / Imad, Nasser / Solomon, Isaac H / Miller, Eric / Riedel, Stefan / Porter, Caroline B M / Villani, Alexandra-Chloé / Tsai, Linus T-Y / Hide, Winston / Szabo, Gyongyi / Hecht, Jonathan / Rozenblatt-Rosen, Orit / Shalek, Alex K / Izar, Benjamin / Regev, Aviv / Popov, Yury / Jiang, Z Gordon / Vlachos, Ioannis S

    bioRxiv : the preprint server for biology

    2022  

    Abstract: The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial ... ...

    Abstract The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
    Language English
    Publishing date 2022-10-28
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.10.27.514070
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies

    Dinnon, Kenneth H / Leist, Sarah R / Okuda, Kenichi / Dang, Hong / Fritch, Ethan J / Gully, Kendra L / Cruz, Gabriela / Evangelista, Mia D / Asakura, Takanori / Gilmore, Rodney C / Hawkins, Padraig / Nakano, Satoko / West, Ande / Schäfer, Alexandra / Gralinski, Lisa E / Everman, Jamie L / Sajuthi, Satria P / Zweigart, Mark R / Dong, Stephanie /
    McBride, Jennifer / Cooley, Michelle R / Hines, Jesse B / Love, Miriya K / Groshong, Steve D / VanSchoiack, Alison / Phelan, Stefan J / Liang, Yan / Hether, Tyler / Leon, Michael / Zumwalt, Ross E / Barton, Lisa M / Duval, Eric J / Mukhopadhyay, Sanjay / Stroberg, Edana / Borczuk, Alain / Thorne, Leigh B / Sakthivel, Muthu K / Lee, Yueh Z / Hagood, James S / Mock, Jason R / Seibold, Max A / O'Neal, Wanda K / Montgomery, Stephanie A / Boucher, Richard C / Baric, Ralph S

    bioRxiv

    Abstract: COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress ... ...

    Abstract COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery. At 15-120 days post-virus clearance, histologic evaluation identified subpleural lesions containing collagen, proliferative fibroblasts, and chronic inflammation with tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal upregulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
    Keywords covid19
    Language English
    Publishing date 2022-02-15
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.02.15.480515
    Database COVID19

    Kategorien

  7. Article ; Online: A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients

    Pita-Juarez, Yered / Karagkouni, Dimitra / Kalavros, Nikolaos / Melms, Johannes C. / Niezen, Sebastian / Delorey, Toni M. / Essene, Adam L / Brook, Olga R. / Pant, Deepti / Skelton-Badlani, Disha / Naderi, Pourya / Huang, Pinzhu / Pan, Liuliu / Hether, Tyler / Andrews, Tallulah S. / Ziegler, Carly G.K. / Reeves, Jason / Myloserdnyy, Andriy / Chen, Rachel /
    Nam, Andy / Phelan, Stefan / Liang, Yan / Amin, Amit Dipak / Biermann, Jana / Hibshoosh, Hanina / Veregge, Molly / Kramer, Zachary / Jacobs, Christopher / Yalcin, Yusuf / Phillips, Devan / Slyper, Michal / Subramanian, Ayshwarya / Ashenberg, Orr / Bloom-Ackermann, Zohar / Tran, Victoria M. / Gomez, James / Sturm, Alexander / Zhang, Shuting / Fleming, Stephen J. / Warren, Sarah / Beechem, Joseph / Hung, Deborah / Babadi, Mehrtash / Padera, Robert F. / MacParland, Sonya A. / Bader, Gary D. / Imad, Nasser / Solomon, Isaac H. / Miller, Eric / Riedel, Stefan / Porter, Caroline B.M. / Villani, Alexandra-Chloé / Tsai, Linus T.-Y. / Hide, Winston / Szabo, Gyongyi / Hecht, Jonathan / Rozenblatt-Rosen, Orit / Shalek, Alex K. / Izar, Benjamin / Regev, Aviv / Popov, Yury / Jiang, Z. Gordon / Vlachos, Ioannis S.

    bioRxiv

    Abstract: The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial ... ...

    Abstract The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
    Keywords covid19
    Language English
    Publishing date 2022-10-28
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.10.27.514070
    Database COVID19

    Kategorien

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