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  1. AU="Rueckert, Erroll H"
  2. AU=Keestra-Gounder A. Marijke
  3. AU="María José Endara"
  4. AU="Li, Lin-Zi"
  5. AU="Shirvanian, Moein"
  6. AU="Capaldo, Bianca D"
  7. AU="Matose, Takunda"
  8. AU=Plouffe Brian D.
  9. AU=Kuter David J
  10. AU="Moore, I D"
  11. AU="Schreibing, Felix"
  12. AU=Kang Keunsoo
  13. AU="de Pedro-Múñez, Álvaro"

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  1. Artikel ; Online: Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection.

    Desai, Niyati / Neyaz, Azfar / Szabolcs, Annamaria / Shih, Angela R / Chen, Jonathan H / Thapar, Vishal / Nieman, Linda T / Solovyov, Alexander / Mehta, Arnav / Lieb, David J / Kulkarni, Anupriya S / Jaicks, Christopher / Xu, Katherine H / Raabe, Michael J / Pinto, Christopher J / Juric, Dejan / Chebib, Ivan / Colvin, Robert B / Kim, Arthur Y /
    Monroe, Robert / Warren, Sarah E / Danaher, Patrick / Reeves, Jason W / Gong, Jingjing / Rueckert, Erroll H / Greenbaum, Benjamin D / Hacohen, Nir / Lagana, Stephen M / Rivera, Miguel N / Sholl, Lynette M / Stone, James R / Ting, David T / Deshpande, Vikram

    Nature communications

    2020  Band 11, Heft 1, Seite(n) 6319

    Abstract: The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein ... ...

    Abstract The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.
    Mesh-Begriff(e) Adult ; Aged ; Aged, 80 and over ; Aspartic Acid Endopeptidases/metabolism ; Autopsy ; COVID-19/immunology ; COVID-19/metabolism ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Epithelial Cells/virology ; Female ; Host Microbial Interactions ; Humans ; Immunity ; Immunohistochemistry ; In Situ Hybridization ; Interferons/genetics ; Interferons/metabolism ; Lung/pathology ; Lung/virology ; Macrophages/immunology ; Male ; Middle Aged ; Mucins/genetics ; Mucins/metabolism ; Surface-Active Agents/metabolism ; Transcriptome ; Viral Load
    Chemische Substanzen Mucins ; Surface-Active Agents ; Interferons (9008-11-1) ; Aspartic Acid Endopeptidases (EC 3.4.23.-) ; NAPSA protein, human (EC 3.4.23.-)
    Sprache Englisch
    Erscheinungsdatum 2020-12-09
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-20139-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  2. Artikel: Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection.

    Desai, Niyati / Neyaz, Azfar / Szabolcs, Annamaria / Shih, Angela R / Chen, Jonathan H / Thapar, Vishal / Nieman, Linda T / Solovyov, Alexander / Mehta, Arnav / Lieb, David J / Kulkarni, Anupriya S / Jaicks, Christopher / Pinto, Christopher J / Juric, Dejan / Chebib, Ivan / Colvin, Robert B / Kim, Arthur Y / Monroe, Robert / Warren, Sarah E /
    Danaher, Patrick / Reeves, Jason W / Gong, Jingjing / Rueckert, Erroll H / Greenbaum, Benjamin D / Hacohen, Nir / Lagana, Stephen M / Rivera, Miguel N / Sholl, Lynette M / Stone, James R / Ting, David T / Deshpande, Vikram

    medRxiv : the preprint server for health sciences

    2020  

    Abstract: The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical ... ...

    Abstract The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter- and intra- patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes. Using a digital spatial profiling platform, the virus corresponded to distinct spatial expression of interferon response genes and immune checkpoint genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-08-02
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2020.07.30.20165241
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  3. Artikel ; Online: Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection

    Desai, Niyati / Neyaz, Azfar / Szabolcs, Annamaria / Shih, Angela R / Chen, Jonathan H / Thapar, Vishal / Nieman, Linda T / Solovyov, Alexander / Mehta, Arnav / Lieb, David J / Kulkarni, Anupriya S / Jaicks, Christopher / Pinto, Christopher J / Juric, Dejan / Chebib, Ivan / Colvin, Robert B / Kim, Arthur Y / Monroe, Robert / Warren, Sarah E /
    Danaher, Patrick / Reeves, Jason W / Gong, Jingjing / Rueckert, Erroll H / Greenbaum, Benjamin D / Hacohen, Nir / Lagana, Stephen M / Rivera, Miguel N / Sholl, Lynette M / Stone, James R / Ting, David T / Deshpande, Vikram

    medRxiv

    Abstract: The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical ... ...

    Abstract The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter- and intra- patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes. Using a digital spatial profiling platform, the virus corresponded to distinct spatial expression of interferon response genes and immune checkpoint genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-08-02
    Verlag Cold Spring Harbor Laboratory Press
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2020.07.30.20165241
    Datenquelle COVID19

    Kategorien

  4. Artikel: A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2.

    Delorey, Toni M / Ziegler, Carly G K / Heimberg, Graham / Normand, Rachelly / Yang, Yiming / Segerstolpe, Asa / Abbondanza, Domenic / Fleming, Stephen J / Subramanian, Ayshwarya / Montoro, Daniel T / Jagadeesh, Karthik A / Dey, Kushal K / Sen, Pritha / Slyper, Michal / Pita-Juárez, Yered H / Phillips, Devan / Bloom-Ackerman, Zohar / Barkas, Nick / Ganna, Andrea /
    Gomez, James / Normandin, Erica / Naderi, Pourya / Popov, Yury V / Raju, Siddharth S / Niezen, Sebastian / Tsai, Linus T-Y / Siddle, Katherine J / Sud, Malika / Tran, Victoria M / Vellarikkal, Shamsudheen K / Amir-Zilberstein, Liat / Atri, Deepak S / Beechem, Joseph / Brook, Olga R / Chen, Jonathan / Divakar, Prajan / Dorceus, Phylicia / Engreitz, Jesse M / Essene, Adam / Fitzgerald, Donna M / Fropf, Robin / Gazal, Steven / Gould, Joshua / Grzyb, John / Harvey, Tyler / Hecht, Jonathan / Hether, Tyler / Jane-Valbuena, Judit / Leney-Greene, Michael / Ma, Hui / McCabe, Cristin / McLoughlin, Daniel E / Miller, Eric M / Muus, Christoph / Niemi, Mari / Padera, Robert / Pan, Liuliu / Pant, Deepti / Pe'er, Carmel / Pfiffner-Borges, Jenna / Pinto, Christopher J / Plaisted, Jacob / Reeves, Jason / Ross, Marty / Rudy, Melissa / Rueckert, Erroll H / Siciliano, Michelle / Sturm, Alexander / Todres, Ellen / Waghray, Avinash / Warren, Sarah / Zhang, Shuting / Zollinger, Daniel R / Cosimi, Lisa / Gupta, Rajat M / Hacohen, Nir / Hide, Winston / Price, Alkes L / Rajagopal, Jayaraj / Tata, Purushothama Rao / Riedel, Stefan / Szabo, Gyongyi / Tickle, Timothy L / Hung, Deborah / Sabeti, Pardis C / Novak, Richard / Rogers, Robert / Ingber, Donald E / Jiang, Z Gordon / Juric, Dejan / Babadi, Mehrtash / Farhi, Samouil L / Stone, James R / Vlachos, Ioannis S / Solomon, Isaac H / Ashenberg, Orr / Porter, Caroline B M / Li, Bo / Shalek, Alex K / Villani, Alexandra-Chloé / Rozenblatt-Rosen, Orit / Regev, Aviv

    bioRxiv : the preprint server for biology

    2021  

    Abstract: The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and ... ...

    Abstract The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellular responses associated with COVID-19 infection, symptoms, and lethality. To address this, we collected tissues from 11 organs during the clinical autopsy of 17 individuals who succumbed to COVID-19, resulting in a tissue bank of approximately 420 specimens. We generated comprehensive cellular maps capturing COVID-19 biology related to patients' demise through single-cell and single-nucleus RNA-Seq of lung, kidney, liver and heart tissues, and further contextualized our findings through spatial RNA profiling of distinct lung regions. We developed a computational framework that incorporates removal of ambient RNA and automated cell type annotation to facilitate comparison with other healthy and diseased tissue atlases. In the lung, we uncovered significantly altered transcriptional programs within the epithelial, immune, and stromal compartments and cell intrinsic changes in multiple cell types relative to lung tissue from healthy controls. We observed evidence of: alveolar type 2 (AT2) differentiation replacing depleted alveolar type 1 (AT1) lung epithelial cells, as previously seen in fibrosis; a concomitant increase in myofibroblasts reflective of defective tissue repair; and, putative TP63
    Sprache Englisch
    Erscheinungsdatum 2021-02-25
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2021.02.25.430130
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  5. Artikel ; Online: COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.

    Delorey, Toni M / Ziegler, Carly G K / Heimberg, Graham / Normand, Rachelly / Yang, Yiming / Segerstolpe, Åsa / Abbondanza, Domenic / Fleming, Stephen J / Subramanian, Ayshwarya / Montoro, Daniel T / Jagadeesh, Karthik A / Dey, Kushal K / Sen, Pritha / Slyper, Michal / Pita-Juárez, Yered H / Phillips, Devan / Biermann, Jana / Bloom-Ackermann, Zohar / Barkas, Nikolaos /
    Ganna, Andrea / Gomez, James / Melms, Johannes C / Katsyv, Igor / Normandin, Erica / Naderi, Pourya / Popov, Yury V / Raju, Siddharth S / Niezen, Sebastian / Tsai, Linus T-Y / Siddle, Katherine J / Sud, Malika / Tran, Victoria M / Vellarikkal, Shamsudheen K / Wang, Yiping / Amir-Zilberstein, Liat / Atri, Deepak S / Beechem, Joseph / Brook, Olga R / Chen, Jonathan / Divakar, Prajan / Dorceus, Phylicia / Engreitz, Jesse M / Essene, Adam / Fitzgerald, Donna M / Fropf, Robin / Gazal, Steven / Gould, Joshua / Grzyb, John / Harvey, Tyler / Hecht, Jonathan / Hether, Tyler / Jané-Valbuena, Judit / Leney-Greene, Michael / Ma, Hui / McCabe, Cristin / McLoughlin, Daniel E / Miller, Eric M / Muus, Christoph / Niemi, Mari / Padera, Robert / Pan, Liuliu / Pant, Deepti / Pe'er, Carmel / Pfiffner-Borges, Jenna / Pinto, Christopher J / Plaisted, Jacob / Reeves, Jason / Ross, Marty / Rudy, Melissa / Rueckert, Erroll H / Siciliano, Michelle / Sturm, Alexander / Todres, Ellen / Waghray, Avinash / Warren, Sarah / Zhang, Shuting / Zollinger, Daniel R / Cosimi, Lisa / Gupta, Rajat M / Hacohen, Nir / Hibshoosh, Hanina / Hide, Winston / Price, Alkes L / Rajagopal, Jayaraj / Tata, Purushothama Rao / Riedel, Stefan / Szabo, Gyongyi / Tickle, Timothy L / Ellinor, Patrick T / Hung, Deborah / Sabeti, Pardis C / Novak, Richard / Rogers, Robert / Ingber, Donald E / Jiang, Z Gordon / Juric, Dejan / Babadi, Mehrtash / Farhi, Samouil L / Izar, Benjamin / Stone, James R / Vlachos, Ioannis S / Solomon, Isaac H / Ashenberg, Orr / Porter, Caroline B M / Li, Bo / Shalek, Alex K / Villani, Alexandra-Chloé / Rozenblatt-Rosen, Orit / Regev, Aviv

    Nature

    2021  Band 595, Heft 7865, Seite(n) 107–113

    Abstract: COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ ... ...

    Abstract COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure
    Mesh-Begriff(e) Adult ; Aged ; Aged, 80 and over ; Atlases as Topic ; Autopsy ; Biological Specimen Banks ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/pathology ; COVID-19/virology ; Endothelial Cells ; Epithelial Cells/pathology ; Epithelial Cells/virology ; Female ; Fibroblasts ; Genome-Wide Association Study ; Heart/virology ; Humans ; Inflammation/pathology ; Inflammation/virology ; Kidney/pathology ; Kidney/virology ; Liver/pathology ; Liver/virology ; Lung/pathology ; Lung/virology ; Male ; Middle Aged ; Myocardium/pathology ; Organ Specificity ; Phagocytes ; Pulmonary Alveoli/pathology ; Pulmonary Alveoli/virology ; RNA, Viral/analysis ; Regeneration ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Single-Cell Analysis ; Viral Load
    Chemische Substanzen RNA, Viral
    Sprache Englisch
    Erscheinungsdatum 2021-04-29
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-021-03570-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  6. Artikel: Promoter choice determines splice site selection in protocadherin alpha and gamma pre-mRNA splicing.

    Tasic, Bosiljka / Nabholz, Christoph E / Baldwin, Kristin K / Kim, Youngwook / Rueckert, Erroll H / Ribich, Scott A / Cramer, Paula / Wu, Qiang / Axel, Richard / Maniatis, Tom

    Molecular cell

    2002  Band 10, Heft 1, Seite(n) 21–33

    Abstract: A family of mammalian protocadherin (Pcdh) proteins is encoded by three closely linked gene clusters (alpha, beta, and gamma). Multiple alpha and gamma Pcdh mRNAs are expressed in distinct patterns in the nervous system and are generated by alternative ... ...

    Abstract A family of mammalian protocadherin (Pcdh) proteins is encoded by three closely linked gene clusters (alpha, beta, and gamma). Multiple alpha and gamma Pcdh mRNAs are expressed in distinct patterns in the nervous system and are generated by alternative pre-mRNA splicing between different "variable" exons and three "constant" exons within each cluster. We show that each Pcdh variable exon is preceded by a promoter and that promoter choice determines which variable exon is included in a Pcdh mRNA. In addition, we provide evidence that alternative splicing of variable exons within a gene cluster occurs via a cis-splicing mechanism. However, virtually every variable exon can engage in trans-splicing with constant exons from another cluster, albeit at a far lower level.
    Mesh-Begriff(e) Alleles ; Alternative Splicing/genetics ; Animals ; Cadherins/genetics ; Exons/genetics ; Humans ; Mice ; Promoter Regions, Genetic/genetics ; Protein Isoforms/genetics ; Protein Precursors/chemistry ; Protein Precursors/genetics ; RNA Precursors/genetics ; RNA Precursors/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Trans-Splicing/genetics ; Transcription, Genetic
    Chemische Substanzen Cadherins ; Protein Isoforms ; Protein Precursors ; RNA Precursors ; RNA, Messenger
    Sprache Englisch
    Erscheinungsdatum 2002-05-09
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/s1097-2765(02)00578-6
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

  7. Artikel ; Online: A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2

    Delorey, Toni M. / Ziegler, Carly G. K. / Heimberg, Graham / Normand, Rachelly / Yang, Yiming / Segerstolpe, Asa / Abbondanza, Domenic / Fleming, Stephen J. / Subramanian, Ayshwarya / Montoro, Daniel T. / Jagadeesh, Karthik A. / Dey, Kushal / Sen, Pritha / Slyper, Michal / Pita-Juarez, Yered / Phillips, Devan / Bloom-Ackermann, Zohar / Barkas, Nick / Ganna, Andrea /
    Gomez, James / Normandin, Erica / Naderi, Pourya / Popov, Yury V. / Raju, Siddharth S. / Niezen, Sebastian / Tsai, Linus T.-Y. / Siddle, Katherine J. / Sud, Malika / Tran, Victoria M. / Karuthedath Vellarikkal, Shamsudheen / Amir-Zilberstein, Liat / Atri, Deepak S. / Beechem, Joseph M / Brook, Olga R. / Chen, Jonathan / Divakar, Prajan / Dorceus, Phylicia / Engreitz, Jesse M / Essene, Adam / Fitzgerald, Donna M. / Fropf, Robin / Gazal, Steven / Gould, Joshua / Grzyb, John / Harvey, Tyler / Hecht, Jonathan / Hether, Tyler / Jane-Valbuena, Judit / Leney-Greene, Michael / Ma, Hui / McCabe, Cristin / McLoughlin, Daniel E. / Miller, Eric M. / Muus, Christoph / Niemi, Mari / Padera, Robert / Pan, Liuliu / Pant, Deepti / Pe'er, Carmel / Pfiffner-Borges, Jenna / Pinto, Christopher J. / Plaisted, Jacob / Reeves, Jason / Ross, Marty / Rudy, Melissa / Rueckert, Erroll H. / Siciliano, Michelle / Sturm, Alexander / Todres, Ellen / Waghray, Avinash / Warren, Sarah / Zhang, Shuting / Zollinger, Dan / Cosimi, Lisa / Gupta, Rajat M / Hacohen, Nir / Hide, Winston / Price, Alkes L. / Rajagopal, Jayaraj / Tata, Purushothama Rao / Riedel, Stefan / Szabo, Gyongyi / Tickle, Timothy L. / Hung, Deborah / Sabeti, Pardis C. / Novak, Richard / Rogers, Robert / Ingber, Donald E. / Jiang, Z Gordon / Juric, Dejan / Babadi, Mehrtash / Farhi, Samouil L. / Stone, James R. / Vlachos, Ioannis S. / Solomon, Isaac H. / Ashenberg, Orr / Porter, Caroline B.M. / Li, Bo / Shalek, Alex K. / Villani, Alexandra-Chloe / Rozenblatt-Rosen, Orit / Regev, Aviv

    bioRxiv

    Abstract: The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and ... ...

    Abstract The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellular responses associated with COVID-19 infection, symptoms, and lethality. To address this, we collected tissues from 11 organs during the clinical autopsy of 17 individuals who succumbed to COVID-19, resulting in a tissue bank of approximately 420 specimens. We generated comprehensive cellular maps capturing COVID-19 biology related to patients demise through single-cell and single-nucleus RNA-Seq of lung, kidney, liver and heart tissues, and further contextualized our findings through spatial RNA profiling of distinct lung regions. We developed a computational framework that incorporates removal of ambient RNA and automated cell type annotation to facilitate comparison with other healthy and diseased tissue atlases. In the lung, we uncovered significantly altered transcriptional programs within the epithelial, immune, and stromal compartments and cell intrinsic changes in multiple cell types relative to lung tissue from healthy controls. We observed evidence of: alveolar type 2 (AT2) differentiation replacing depleted alveolar type 1 (AT1) lung epithelial cells, as previously seen in fibrosis; a concomitant increase in myofibroblasts reflective of defective tissue repair; and, putative TP63+ intrapulmonary basal-like progenitor (IPBLP) cells, similar to cells identified in H1N1 influenza, that may serve as an emergency cellular reserve for severely damaged alveoli. Together, these findings suggest the activation and failure of multiple avenues for regeneration of the epithelium in these terminal lungs. SARS-CoV-2 RNA reads were enriched in lung mononuclear phagocytic cells and endothelial cells, and these cells expressed distinct host response transcriptional programs. We corroborated the compositional and transcriptional changes in lung tissue through spatial analysis of RNA profiles in situ and distinguished unique tissue host responses between regions with and without viral RNA, and in COVID-19 donor tissues relative to healthy lung. Finally, we analyzed genetic regions implicated in COVID-19 GWAS with transcriptomic data to implicate specific cell types and genes associated with disease severity. Overall, our COVID-19 cell atlas is a foundational dataset to better understand the biological impact of SARS-CoV-2 infection across the human body and empowers the identification of new therapeutic interventions and prevention strategies.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2021-02-25
    Verlag Cold Spring Harbor Laboratory
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2021.02.25.430130
    Datenquelle COVID19

    Kategorien

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