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4. Human SARS-CoV-2 challenge uncovers local and systemic response dynamics

Author

Lindeboom, Rik G. H., Worlock, Kaylee B., Dratva, Lisa M., Yoshida, Masahiro, Scobie, David, Wagstaffe, Helen R., Richardson, Laura, Wilbrey-Clark, Anna, Barnes, Josephine L., Kretschmer, Lorenz, Polanski, Krzysztof, Allen-Hyttinen, Jessica, Mehta, Puja, Sumanaweera, Dinithi, Boccacino, Jacqueline M., Sungnak, Waradon, Elmentaite, Rasa, Huang, Ni, Mamanova, Lira, Kapuge, Rakesh, Bolt, Liam, Prigmore, Elena, Killingley, Ben, Kalinova, Mariya, Mayer, Maria, Boyers, Alison, Mann, Alex, Swadling, Leo, Woodall, Maximillian N. J., Ellis, Samuel, Smith, Claire M., Teixeira, Vitor H., Janes, Sam M., Chambers, Rachel C., Haniffa, Muzlifah, Catchpole, Andrew, Heyderman, Robert, Noursadeghi, Mahdad, Chain, Benny, Mayer, Andreas, Meyer, Kerstin B., Chiu, Christopher, Nikolić, Marko Z., and Teichmann, Sarah A.

Published
2024
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7. Early human lung immune cell development and its role in epithelial cell fate.

Author

Barnes, Josephine, Yoshida, Masahiro, He, Peng, Worlock, Kaylee, Lindeboom, Rik, Suo, Chenqu, Pett, J, Wilbrey-Clark, Anna, Dann, Emma, Mamanova, Lira, Richardson, Laura, Polanski, Krzysztof, Pennycuick, Adam, Allen-Hyttinen, Jessica, Herczeg, Iván, Arzili, Romina, Hynds, Robert, Teixeira, Vitor, Haniffa, Muzlifah, Lim, Kyungtae, Sun, Dawei, Rawlins, Emma, Oliver, Amanda, Lyons, Paul, Marioni, John, Ruhrberg, Christiana, Tuong, Zewen, Clatworthy, Menna, Reading, James, Janes, Sam, Teichmann, Sarah, Meyer, Kerstin, and Nikolić, Marko

Subjects
Humans, Immunity, Innate, Cell Differentiation, Lung, Killer Cells, Natural, Epithelial Cells
Abstract

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development.

Published
2023

12. An integrated cell atlas of the lung in health and disease

Author

Sikkema, Lisa, Ramírez-Suástegui, Ciro, Strobl, Daniel C, Gillett, Tessa E, Zappia, Luke, Madissoon, Elo, Markov, Nikolay S, Zaragosi, Laure-Emmanuelle, Ji, Yuge, Ansari, Meshal, Arguel, Marie-Jeanne, Apperloo, Leonie, Banchero, Martin, Bécavin, Christophe, Berg, Marijn, Chichelnitskiy, Evgeny, Chung, Mei-i, Collin, Antoine, Gay, Aurore CA, Gote-Schniering, Janine, Hooshiar Kashani, Baharak, Inecik, Kemal, Jain, Manu, Kapellos, Theodore S, Kole, Tessa M, Leroy, Sylvie, Mayr, Christoph H, Oliver, Amanda J, von Papen, Michael, Peter, Lance, Taylor, Chase J, Walzthoeni, Thomas, Xu, Chuan, Bui, Linh T, De Donno, Carlo, Dony, Leander, Faiz, Alen, Guo, Minzhe, Gutierrez, Austin J, Heumos, Lukas, Huang, Ni, Ibarra, Ignacio L, Jackson, Nathan D, Kadur Lakshminarasimha Murthy, Preetish, Lotfollahi, Mohammad, Tabib, Tracy, Talavera-López, Carlos, Travaglini, Kyle J, Wilbrey-Clark, Anna, Worlock, Kaylee B, Yoshida, Masahiro, van den Berge, Maarten, Bossé, Yohan, Desai, Tushar J, Eickelberg, Oliver, Kaminski, Naftali, Krasnow, Mark A, Lafyatis, Robert, Nikolic, Marko Z, Powell, Joseph E, Rajagopal, Jayaraj, Rojas, Mauricio, Rozenblatt-Rosen, Orit, Seibold, Max A, Sheppard, Dean, Shepherd, Douglas P, Sin, Don D, Timens, Wim, Tsankov, Alexander M, Whitsett, Jeffrey, Xu, Yan, Banovich, Nicholas E, Barbry, Pascal, Duong, Thu Elizabeth, Falk, Christine S, Meyer, Kerstin B, Kropski, Jonathan A, Pe’er, Dana, Schiller, Herbert B, Tata, Purushothama Rao, Schultze, Joachim L, Teichmann, Sara A, Misharin, Alexander V, Nawijn, Martijn C, Luecken, Malte D, and Theis, Fabian J

Subjects
Lung, Genetics, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Respiratory, Good Health and Well Being, Humans, COVID-19, Pulmonary Fibrosis, Lung Neoplasms, Macrophages, Lung Biological Network Consortium, Medical and Health Sciences, Immunology
Abstract

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.

Published
2023

17. Author Correction: Human SARS-CoV-2 challenge uncovers local and systemic response dynamics

Author

Lindeboom, Rik G. H., Worlock, Kaylee B., Dratva, Lisa M., Yoshida, Masahiro, Scobie, David, Wagstaffe, Helen R., Richardson, Laura, Wilbrey-Clark, Anna, Barnes, Josephine L., Kretschmer, Lorenz, Polanski, Krzysztof, Allen-Hyttinen, Jessica, Mehta, Puja, Sumanaweera, Dinithi, Boccacino, Jacqueline M., Sungnak, Waradon, Elmentaite, Rasa, Huang, Ni, Mamanova, Lira, Kapuge, Rakesh, Bolt, Liam, Prigmore, Elena, Killingley, Ben, Kalinova, Mariya, Mayer, Maria, Boyers, Alison, Mann, Alex, Swadling, Leo, Woodall, Maximillian N. J., Ellis, Samuel, Smith, Claire M., Teixeira, Vitor H., Janes, Sam M., Chambers, Rachel C., Haniffa, Muzlifah, Catchpole, Andrew, Heyderman, Robert, Noursadeghi, Mahdad, Chain, Benny, Mayer, Andreas, Meyer, Kerstin B., Chiu, Christopher, Nikolić, Marko Z., and Teichmann, Sarah A.

Published
2024
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23. A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.

Author

Madissoon, Elo, Oliver, Amanda, Kleshchevnikov, Vitalii, Wilbrey-Clark, Anna, Polanski, Krzysztof, Richoz, Nathan, Ribeiro Orsi, Ana, Mamanova, Lira, Bolt, Liam, Elmentaite, Rasa, Pett, J, Huang, Ni, Xu, Chuan, He, Peng, Dabrowska, Monika, Pritchard, Sophie, Tuck, Liz, Prigmore, Elena, Perera, Shani, Knights, Andrew, Oszlanczi, Agnes, Hunter, Adam, Vieira, Sara, Patel, Minal, Lindeboom, Rik, Campos, Lia, Matsuo, Kazuhiko, Nakayama, Takashi, Yoshida, Masahiro, Worlock, Kaylee, Nikolić, Marko, Georgakopoulos, Nikitas, Mahbubani, Krishnaa, Saeb-Parsy, Kourosh, Bayraktar, Omer, Clatworthy, Menna, Stegle, Oliver, Kumasaka, Natsuhiko, Teichmann, Sarah, and Meyer, Kerstin

Subjects
Humans, Respiratory Mucosa, Lung, Epithelial Cells, B-Lymphocytes, Immunoglobulin A
Abstract

Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new gland-associated immune niche has implications for respiratory health.

Published
2023

24. Exploring the value of a global gene drive project registry

Author

Taitingfong, Riley I, Triplett, Cynthia, Vásquez, Váleri N, Rajagopalan, Ramya M, Raban, Robyn, Roberts, Aaron, Terradas, Gerard, Baumgartner, Bridget, Emerson, Claudia, Gould, Fred, Okumu, Fredros, Schairer, Cynthia E, Bossin, Hervé C, Buchman, Leah, Campbell, Karl J, Clark, Anna, Delborne, Jason, Esvelt, Kevin, Fisher, Joshua, Friedman, Robert M, Gronvall, Gigi, Gurfield, Nikos, Heitman, Elizabeth, Kofler, Natalie, Kuiken, Todd, Kuzma, Jennifer, Manrique-Saide, Pablo, Marshall, John M, Montague, Michael, Morrison, Amy C, Opesen, Chris C, Phelan, Ryan, Piaggio, Antoinette, Quemada, Hector, Rudenko, Larisa, Sawadogo, Natéwindé, Smith, Robert, Tuten, Holly, Ullah, Anika, Vorsino, Adam, Windbichler, Nikolai, Akbari, Omar S, Long, Kanya, Lavery, James V, Evans, Sam Weiss, Tountas, Karen, and Bloss, Cinnamon S

Subjects
Gene Drive Technology, Registries, Data Collection
Published
2023

31. Spatially resolved multiomics of human cardiac niches

Author

Kanemaru, Kazumasa, Cranley, James, Muraro, Daniele, Miranda, Antonio M. A., Ho, Siew Yen, Wilbrey-Clark, Anna, Patrick Pett, Jan, Polanski, Krzysztof, Richardson, Laura, Litvinukova, Monika, Kumasaka, Natsuhiko, Qin, Yue, Jablonska, Zuzanna, Semprich, Claudia I., Mach, Lukas, Dabrowska, Monika, Richoz, Nathan, Bolt, Liam, Mamanova, Lira, Kapuge, Rakeshlal, Barnett, Sam N., Perera, Shani, Talavera-López, Carlos, Mulas, Ilaria, Mahbubani, Krishnaa T., Tuck, Liz, Wang, Lu, Huang, Margaret M., Prete, Martin, Pritchard, Sophie, Dark, John, Saeb-Parsy, Kourosh, Patel, Minal, Clatworthy, Menna R., Hübner, Norbert, Chowdhury, Rasheda A., Noseda, Michela, and Teichmann, Sarah A.

Published
2023
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49. Preparing to Lead: Lessons in Principal Development from High-Performing Education Systems

Author

National Center on Education and the Economy (NCEE), National Center on Education and the Economy (NCEE), Center on International Education Benchmarking (CIEB), Jensen, Ben, Downing, Phoebe, and Clark, Anna

Abstract

This report focuses on how four high-performing systems of education designed and deliver high-quality leadership development programs for aspiring principals. While these systems have a strategic, system-wide approach that positions programs within the broader continuum of leadership development, this report focuses on programs that prepare aspiring principals for their future roles and responsibilities. It begins with an overview of the latest research in leadership, which is primarily focused on business leadership. It finds that the best business research programs have the same characteristics as school leadership programs in the top-performing countries: they are highly contextualized and engage leaders in addressing real problems. The report finds, in fact, that some education systems can provide leadership development programs that far surpass those for generalist or executive MBAs. The world's highest-performing school systems have all made extensive investments in school leadership development programs, and these provide some insights. Students in Ontario, Singapore, Hong Kong and Shanghai performed, on average, in the global top ten systems for student achievement in mathematics, literacy and science in the Programme for International Student Assessment (PISA) for 2009 and 2012. But these systems have not always been at the top of the world tables. This report shows how these systems now provide high-quality school leadership development programs that: (1) Are tailored to reforms in each specific education system, so that programs vary to deliver the school leadership that each system needs; (2) Design the training as a practical experience under the guidance of expert leaders; and (3) Overcome the pitfalls of both leadership development in other industries and generalist and executive MBA programs. [The analysis presented in this report was conducted by Learning First.]

Published
2017

50. Alternative Histories of the Self

Author

Clark, Anna

Subjects
Edith Ellis, Chevalier d'Eon, transgender, history of sexuality, lesbian history, LGBTQIA+ history, Anne Lister, James Hinton, Richard Johnson, gender history, polygamy, unique self, sexual transgression, social conventions, social history, empire, coded diaries, diplomat, individual, non conformity, queer history, ethics, social justice, political traditions, relationships, secrets, privacy, same-sex desire, men, women, thema EDItEUR::D Biography, Literature and Literary studies::DN Biography and non-fiction prose::DNC Memoirs, thema EDItEUR::N History and Archaeology::NH History::NHD European history, thema EDItEUR::N History and Archaeology, thema EDItEUR::3 Time period qualifiers::3M c 1500 onwards to present day, thema EDItEUR::J Society and Social Sciences::JB Society and culture: general::JBS Social groups, communities and identities::JBSF Gender studies, gender groups
Abstract

This open access book investigates how people re-imagined the idea of the unique self in the period from 1762 to 1917. Some used the notion of the unique self to justify their gender and sexual transgression, but others rejected the notion of the unique self and instead demanded the sacrifice of the self for the good of society. The substantial introductory chapter places these themes in the cultural context of the long nineteenth century, but the book as a whole represents an alternative method for studying the self. Instead of focusing on the thoughts of great thinkers, this book explores how five unusual individuals twisted conventional ideas of the self as they interpreted their own lives. These subjects include: * The Chevalièr/e d’Eon, a renegade diplomat who was outed as a woman * Anne Lister, who wrote coded diaries about her attraction to women * Richard Johnson, who secretly criticized the empire that he served * James Hinton, a Victorian doctor who publicly advocated philanthropy and privately supported polygamy * Edith Ellis, a socialist lesbian who celebrated the ‘abnormal’ These five case studies are skilfully used to explore how the notion of the unique individual was used to make sense of sexual or gender non-conformity. Yet this queer reading will go beyond same-sex desire to analyse the issue of secrets and privacy; for instance, what stigma did men who practiced or advocated unconventional relationships with women incur? Finally, Clark ties these unusual lives to the wider questions of ethics and social justice: did those who questioned sexual conventions challenge political traditions as well? This is a highly innovative study that will be of interest to intellectual historians of modern Britain and Europe, as well as historians of gender and sexuality. The ebook editions of this book are available open access under a CC BY-NC-ND 4.0 licence on bloomsburycollections.com. Open access was funded by Knowledge Unlatched.

Published
2017

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