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2. A roadmap for the Human Developmental Cell Atlas

Author

Haniffa, Muzlifah, Taylor, Deanne, Linnarsson, Sten, Aronow, Bruce J, Bader, Gary D, Barker, Roger A, Camara, Pablo G, Camp, J Gray, Chédotal, Alain, Copp, Andrew, Etchevers, Heather C, Giacobini, Paolo, Göttgens, Berthold, Guo, Guoji, Hupalowska, Ania, James, Kylie R, Kirby, Emily, Kriegstein, Arnold, Lundeberg, Joakim, Marioni, John C, Meyer, Kerstin B, Niakan, Kathy K, Nilsson, Mats, Olabi, Bayanne, Pe’er, Dana, Regev, Aviv, Rood, Jennifer, Rozenblatt-Rosen, Orit, Satija, Rahul, Teichmann, Sarah A, Treutlein, Barbara, Vento-Tormo, Roser, and Webb, Simone

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Regenerative Medicine, Stem Cell Research - Nonembryonic - Human, Stem Cell Research, Pediatric, Stem Cell Research - Embryonic - Human, Human Fetal Tissue, Genetics, Human Genome, Good Health and Well Being, Adult, Animals, Atlases as Topic, Cell Culture Techniques, Cell Movement, Cell Survival, Cell Tracking, Cells, Data Visualization, Developmental Biology, Embryo, Mammalian, Female, Fetus, Humans, Imaging, Three-Dimensional, Information Dissemination, Male, Models, Animal, Organogenesis, Organoids, Stem Cells, Human Cell Atlas Developmental Biological Network, General Science & Technology
Abstract

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.

Published
2021

3. Toward a feminist ethic of the self in dialogue with Mary Astell and Michel Foucault

Author

Webb, Simone

Subjects
305.42
Abstract

This thesis puts the later work of Michael Foucault (1926-1984) into dialogue with the early-modern feminist philosopher Mary Astell (1666-1731). I read Astell's key texts through the framework of care of the self and ethic of the self which Foucault develops in his later lectures, interviews, and other texts. I show how she is situated within the same tradition which Foucault identifies in the history of philosophy while at the same time gendering that tradition and turning it to feminist ends. Through my reading of the two philosophers I consider what they can offer a modern feminist ethic of the self. I draw out the potential of Astell's regimen for women in the modern world, using its limitations as opportunities to interrogate and develop. My argument is that we could, today, benefit from a feminism which focuses on women's ethical selves, and a structured askesis to facilitate self-transformation. The thesis comprises five chapters. Chapter One reads Astell's Serious Proposal through Foucault's lens of "care of the self", arguing that Astell presents a feminist ethic of care for the self. Chapter Two examines Astell's "practices of the self", attending especially to her bodily practices and her practices of withdrawal and meditation. Chapter Three concerns philosophy as a spirituality and critical practice of the self in Astell's work. Chapter Four addresses the relationship between self and other in Astell and Foucault, focusing particularly on the role of friendship as fundamental to an ethic of the self. Chapter Five considers the role of religion in Astell's ethic of the self. Each chapter considers the relationship between Astell's ethic and comparable modern experiences. I conclude by considering a possible model for a feminist ethic of the self drawn from Astell's regimen, and by offering a critique of the project as a whole.

Published
2021

5. Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia

Author

Khabirova, Eleonora, Jardine, Laura, Coorens, Tim H. H., Webb, Simone, Treger, Taryn D., Engelbert, Justin, Porter, Tarryn, Prigmore, Elena, Collord, Grace, Piapi, Alice, Teichmann, Sarah A., Inglott, Sarah, Williams, Owen, Heidenreich, Olaf, Young, Matthew D., Straathof, Karin, Bomken, Simon, Bartram, Jack, Haniffa, Muzlifah, and Behjati, Sam

Published
2022
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6. Blood and immune development in human fetal bone marrow and Down syndrome

Author

Jardine, Laura, Webb, Simone, Goh, Issac, Quiroga Londoño, Mariana, Reynolds, Gary, Mather, Michael, and Olabi, Bayanne

Subjects
Physiological aspects, Genetic aspects, Health aspects, Bone marrow -- Physiological aspects -- Health aspects, Hematopoiesis -- Genetic aspects -- Health aspects, Down syndrome -- Physiological aspects, Fetal development -- Health aspects, Immune system -- Physiological aspects -- Health aspects -- Genetic aspects, Fetus -- Growth
Abstract

Author(s): Laura Jardine [sup.1] [sup.2] , Simone Webb [sup.1] , Issac Goh [sup.1] , Mariana Quiroga Londoño [sup.3] , Gary Reynolds [sup.1] , Michael Mather [sup.1] , Bayanne Olabi [sup.1] [...], Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception.sup.1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21). A single-cell atlas of human fetal bone marrow in healthy fetuses and fetuses with Down syndrome provides insight into developmental haematopoiesis in humans and the transcription and functional differences that occur in Down syndrome.

Published
2021
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8. Decoding human fetal liver haematopoiesis

Author

Popescu, Dorin-Mirel, Botting, Rachel A., Stephenson, Emily, Green, Kile, Webb, Simone, Jardine, Laura, and Calderbank, Emily F.

Subjects
Identification and classification, Genetic aspects, Methods, DNA identification -- Methods, Hematopoiesis -- Methods, Fetal tissues -- Identification and classification -- Genetic aspects, Hepatocytes -- Identification and classification, Liver cells -- Identification and classification, DNA testing -- Methods
Abstract

Author(s): Dorin-Mirel Popescu [sup.1] , Rachel A. Botting [sup.1] , Emily Stephenson [sup.1] , Kile Green [sup.1] , Simone Webb [sup.1] , Laura Jardine [sup.1] , Emily F. Calderbank [sup.2] [...], Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs. Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.

Published
2019
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9. Single cell transcriptomics reveals chondrocyte differentiation dynamics in vivo and in vitro

Author

Lawrence, John E G, primary, Woods, Steven, additional, Roberts, Kenny, additional, Sumanaweera, Dinithi N, additional, Balogh, Petra, additional, Predeus, Alexander V, additional, He, Peng, additional, Li, Tong, additional, Polanski, Krzysztof, additional, Prigmore, Elena, additional, Tuck, Elizabeth, additional, Mamanova, Lira, additional, Zhou, Di, additional, Webb, Simone, additional, Jardine, Laura, additional, He, Xiaoling, additional, Barker, Roger A, additional, Haniffa, Muzlifah, additional, Flanagan, Adrienne M, additional, Young, Matthew D, additional, Behjati, Sam, additional, Bayraktar, Omer, additional, Kimber, Susan J, additional, and Teichmann, Sarah, additional

Published
2023
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10. Yolk sac cell atlas reveals multiorgan functions during human early development

Author

Goh, Issac, primary, Botting, Rachel A., additional, Rose, Antony, additional, Webb, Simone, additional, Engelbert, Justin, additional, Gitton, Yorick, additional, Stephenson, Emily, additional, Quiroga Londoño, Mariana, additional, Mather, Michael, additional, Mende, Nicole, additional, Imaz-Rosshandler, Ivan, additional, Yang, Lu, additional, Horsfall, Dave, additional, Basurto-Lozada, Daniela, additional, Chipampe, Nana-Jane, additional, Rook, Victoria, additional, Lee, Jimmy Tsz Hang, additional, Ton, Mai-Linh, additional, Keitley, Daniel, additional, Mazin, Pavel, additional, Vijayabaskar, M. S., additional, Hannah, Rebecca, additional, Gambardella, Laure, additional, Green, Kile, additional, Ballereau, Stephane, additional, Inoue, Megumi, additional, Tuck, Elizabeth, additional, Lorenzi, Valentina, additional, Kwakwa, Kwasi, additional, Alsinet, Clara, additional, Olabi, Bayanne, additional, Miah, Mohi, additional, Admane, Chloe, additional, Popescu, Dorin-Mirel, additional, Acres, Meghan, additional, Dixon, David, additional, Ness, Thomas, additional, Coulthard, Rowen, additional, Lisgo, Steven, additional, Henderson, Deborah J., additional, Dann, Emma, additional, Suo, Chenqu, additional, Kinston, Sarah J., additional, Park, Jong-eun, additional, Polanski, Krzysztof, additional, Marioni, John, additional, van Dongen, Stijn, additional, Meyer, Kerstin B., additional, de Bruijn, Marella, additional, Palis, James, additional, Behjati, Sam, additional, Laurenti, Elisa, additional, Wilson, Nicola K., additional, Vento-Tormo, Roser, additional, Chédotal, Alain, additional, Bayraktar, Omer, additional, Roberts, Irene, additional, Jardine, Laura, additional, Göttgens, Berthold, additional, Teichmann, Sarah A., additional, and Haniffa, Muzlifah, additional

Published
2023
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13. 3159 – A SINGLE-CELL PROTEIN-TRANSCRIPTOME ATLAS OF HAEMATOPOIESIS ACROSS THE HUMAN LIFESPAN

Author

Londoño, Mariana Quiroga, primary, Mende, Nicole, additional, Stephenson, Emily, additional, Iskander, Deena, additional, Isobe, Tomoya, additional, Webb, Simone, additional, Goh, Issac, additional, Shanmugiah, Vijaya Mahalingam, additional, Hannah, Rebecca, additional, Roy, Anindita, additional, Roberts, Irene, additional, Laurenti, Elisa, additional, Haniffa, Muzlifah, additional, Wilson, Nicola K, additional, and Göttgens, Berthold, additional

Published
2023
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14. Single-cell multi-omics analysis of the immune response in COVID-19

Author

Stephenson, Emily, Reynolds, Gary, Botting, Rachel A., Calero-Nieto, Fernando J., Morgan, Michael D., Tuong, Zewen Kelvin, Bach, Karsten, Sungnak, Waradon, Worlock, Kaylee B., Yoshida, Masahiro, Kumasaka, Natsuhiko, Kania, Katarzyna, Engelbert, Justin, Olabi, Bayanne, Spegarova, Jarmila Stremenova, Wilson, Nicola K., Mende, Nicole, Jardine, Laura, Gardner, Louis C. S., Goh, Issac, Horsfall, Dave, McGrath, Jim, Webb, Simone, Mather, Michael W., Lindeboom, Rik G. H., Dann, Emma, Huang, Ni, Polanski, Krzysztof, Prigmore, Elena, Gothe, Florian, Scott, Jonathan, Payne, Rebecca P., Baker, Kenneth F., Hanrath, Aidan T., Schim van der Loeff, Ina C. D., Barr, Andrew S., Sanchez-Gonzalez, Amada, Bergamaschi, Laura, Mescia, Federica, Barnes, Josephine L., Kilich, Eliz, de Wilton, Angus, Saigal, Anita, Saleh, Aarash, Janes, Sam M., Smith, Claire M., Gopee, Nusayhah, Wilson, Caroline, Coupland, Paul, Coxhead, Jonathan M., Kiselev, Vladimir Yu, van Dongen, Stijn, Bacardit, Jaume, King, Hamish W., Rostron, Anthony J., Simpson, A. John, Hambleton, Sophie, Laurenti, Elisa, Lyons, Paul A., Meyer, Kerstin B., Nikolić, Marko Z., Duncan, Christopher J. A., Smith, Kenneth G. C., Teichmann, Sarah A., Clatworthy, Menna R., Marioni, John C., Göttgens, Berthold, and Haniffa, Muzlifah

Subjects
Proteome, COVID-19, Cross-Sectional Studies, Humans, Monocytes, Receptors, Antigen, B-Cell, Receptors, Antigen, T-Cell, SARS-CoV-2, Single-Cell Analysis, T-Lymphocytes, Transcriptome, CD34, Biology, Peripheral blood mononuclear cell, Article, General Biochemistry, Genetics and Molecular Biology, Immune system, Antigen, Receptors, Platelet activation, Progenitor cell, B-Cell, RNA sequencing, General Medicine, T-Cell, Haematopoiesis, Viral infection, Immunology, Infection, CD8
Abstract

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy., Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Published
2021
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15. Multi-organ functions of yolk sac during human early development

Author

Botting, Rachel A, primary, Goh, Issac, additional, Rose, Antony, additional, Webb, Simone, additional, Engelbert, Justin, additional, Gitton, Yorick, additional, Stephenson, Emily, additional, Quiroga Londoño, Mariana, additional, Mather, Michael, additional, Mende, Nicole, additional, Imaz-Rosshandler, Ivan, additional, Horsfall, Dave, additional, Basurto-Lozada, Daniela, additional, Chipampe, Nana-Jane, additional, Rook, Victoria, additional, Mazin, Pavel, additional, Vijayabaskar, MS, additional, Hannah, Rebecca, additional, Gambardella, Laure, additional, Green, Kile, additional, Ballereau, Stephane, additional, Inoue, Megumi, additional, Tuck, Liz, additional, Lorenzi, Valentina, additional, Kwakwa, Kwasi, additional, Alsinet, Clara, additional, Olabi, Bayanne, additional, Miah, Mohi, additional, Admane, Chloe, additional, Popescu, Dorin-Mirel, additional, Acres, Meghan, additional, Dixon, David, additional, Coulthard, Rowen, additional, Lisgo, Steven, additional, Henderson, Deborah J, additional, Dann, Emma, additional, Suo, Chenqu, additional, Kinston, Sarah J, additional, Park, Jong-eun, additional, Polanski, Krzysztof, additional, Van Dongen, Stijn, additional, Meyer, Kerstin B, additional, de Bruijn, Marella, additional, Palis, James, additional, Behjati, Sam, additional, Laurenti, Elisa, additional, Wilson, Nicola K, additional, Vento-Tormo, Roser, additional, Chédotal, Alain, additional, Bayraktar, Omer, additional, Roberts, Irene, additional, Jardine, Laura, additional, Göttgens, Berthold, additional, Teichmann, Sarah A, additional, and Haniffa, Muzlifah, additional

Published
2022
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16. 3107 – MULTI-ORGAN FUNCTIONS OF YOLK SAC DURING HUMAN EARLY DEVELOPMENT

Author

Jardine, Laura, primary, Botting, Rachel, additional, Goh, Issac, additional, Rose, Antony, additional, Webb, Simone, additional, Londoño, Mariana Quiroga, additional, Stephenson, Emily, additional, Engelbert, Justin, additional, Roberts, Irene, additional, Göttgens, Berthold, additional, Teichmann, Sarah, additional, and Haniffa, Muzlifah, additional

Published
2022
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17. 3166 – A PROTEIN‐TRANSCRIPTOME ATLAS OF HAEMATOPOIESIS ACROSS THE HUMAN LIFESPAN

Author

Londoño, Mariana Quiroga, primary, Mende, Nicole, additional, Stephenson, Emily, additional, Iskander, Deena, additional, Webb, Simone, additional, Goh, Issac, additional, Shanmugiah, Vijaya Mahalingam, additional, Roy, Anindita, additional, Roberts, Irene, additional, Laurenti, Elisa, additional, Haniffa, Muzlifah, additional, Wilson, Nicola K, additional, and Göttgens, Berthold, additional

Published
2022
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18. Single cell mRNA signals reveal a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia

Author

Khabirova, Eleonora, primary, Jardine, Laura, additional, Coorens, Tim H. H., additional, Webb, Simone, additional, Treger, Taryn D., additional, Englebert, Justin, additional, Porter, Tarryn, additional, Prigmore, Elena, additional, Collord, Grace, additional, Piapi, Alice, additional, Teichmann, Sarah, additional, Inglott, Sarah, additional, Williams, Owen, additional, Heidenreich, Olaf, additional, Young, Matthew D., additional, Straathof, Karin, additional, Bomken, Simon, additional, Bartram, Jack, additional, Haniffa, Muzlifah, additional, and Behjati, Sam, additional

Published
2021
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20. Intrinsic and extrinsic regulation of human fetal bone marrow haematopoiesis and perturbations in Down syndrome

Author

Jardine, Laura, primary, Webb, Simone, additional, Goh, Issac, additional, Londoño, Mariana Quiroga, additional, Reynolds, Gary, additional, Mather, Michael, additional, Olabi, Bayanne, additional, Stephenson, Emily, additional, Botting, Rachel A., additional, Horsfall, Dave, additional, Engelbert, Justin, additional, Maunder, Daniel, additional, Mende, Nicole, additional, Murnane, Caitlin, additional, Dann, Emma, additional, McGrath, Jim, additional, King, Hamish, additional, Kucinski, Iwo, additional, Queen, Rachel, additional, Carey, Christopher D, additional, Shrubsole, Caroline, additional, Poyner, Elizabeth, additional, Acres, Meghan, additional, Jones, Claire, additional, Ness, Thomas, additional, Coulthard, Rowan, additional, Elliott, Natalina, additional, O’Byrne, Sorcha, additional, Haltalli, Myriam L. R., additional, Lawrence, John E, additional, Lisgo, Steven, additional, Balogh, Petra, additional, Meyer, Kerstin B, additional, Prigmore, Elena, additional, Ambridge, Kirsty, additional, Jain, Mika Sarkin, additional, Efremova, Mirjana, additional, Pickard, Keir, additional, Creasey, Thomas, additional, Bacardit, Jaume, additional, Henderson, Deborah, additional, Coxhead, Jonathan, additional, Filby, Andrew, additional, Hussain, Rafiqul, additional, Dixon, David, additional, McDonald, David, additional, Popescu, Dorin-Mirel, additional, Kowalczyk, Monika S., additional, Li, Bo, additional, Ashenberg, Orr, additional, Tabaka, Marcin, additional, Dionne, Danielle, additional, Tickle, Timothy L., additional, Slyper, Michal, additional, Rozenblatt-Rosen, Orit, additional, Regev, Aviv, additional, Behjati, Sam, additional, Laurenti, Elisa, additional, Wilson, Nicola K., additional, Roy, Anindita, additional, Göttgens, Berthold, additional, Roberts, Irene, additional, Teichmann, Sarah A., additional, and Haniffa, Muzlifah, additional

Published
2021
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22. Developmental cell programs are co-opted in inflammatory skin disease

Author

Reynolds, Gary, primary, Vegh, Peter, additional, Fletcher, James, additional, Poyner, Elizabeth F. M., additional, Stephenson, Emily, additional, Goh, Issac, additional, Botting, Rachel A., additional, Huang, Ni, additional, Olabi, Bayanne, additional, Dubois, Anna, additional, Dixon, David, additional, Green, Kile, additional, Maunder, Daniel, additional, Engelbert, Justin, additional, Efremova, Mirjana, additional, Polański, Krzysztof, additional, Jardine, Laura, additional, Jones, Claire, additional, Ness, Thomas, additional, Horsfall, Dave, additional, McGrath, Jim, additional, Carey, Christopher, additional, Popescu, Dorin-Mirel, additional, Webb, Simone, additional, Wang, Xiao-nong, additional, Sayer, Ben, additional, Park, Jong-Eun, additional, Negri, Victor A., additional, Belokhvostova, Daria, additional, Lynch, Magnus D., additional, McDonald, David, additional, Filby, Andrew, additional, Hagai, Tzachi, additional, Meyer, Kerstin B., additional, Husain, Akhtar, additional, Coxhead, Jonathan, additional, Vento-Tormo, Roser, additional, Behjati, Sam, additional, Lisgo, Steven, additional, Villani, Alexandra-Chloé, additional, Bacardit, Jaume, additional, Jones, Philip H., additional, O’Toole, Edel A., additional, Ogg, Graham S., additional, Rajan, Neil, additional, Reynolds, Nick J., additional, Teichmann, Sarah A., additional, Watt, Fiona M., additional, and Haniffa, Muzlifah, additional

Published
2021
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23. Poised cell circuits in human skin are activated in disease

Author

Reynolds, Gary, primary, Vegh, Peter, additional, Fletcher, James, additional, Poyner, Elizabeth F.M., additional, Stephenson, Emily, additional, Goh, Issac, additional, Botting, Rachel A., additional, Huang, Ni, additional, Olabi, Bayanne, additional, Dubois, Anna, additional, Dixon, David, additional, Green, Kile, additional, Maunder, Daniel, additional, Engelbert, Justin, additional, Efremova, Mirjana, additional, Polański, Krzysztof, additional, Jardine, Laura, additional, Jones, Claire, additional, Ness, Thomas, additional, Horsfall, Dave, additional, McGrath, Jim, additional, Carey, Christopher, additional, Popescu, Dorin-Mirel, additional, Webb, Simone, additional, Wang, Xiao-nong, additional, Sayer, Ben, additional, Park, Jong-Eun, additional, Negri, Victor A., additional, Belokhvostova, Daria, additional, Lynch, Magnus, additional, McDonald, David, additional, Filby, Andrew, additional, Hagai, Tzachi, additional, Meyer, Kerstin B., additional, Husain, Akhtar, additional, Coxhead, Jonathan, additional, Vento-Tormo, Roser, additional, Behjati, Sam, additional, Lisgo, Steven, additional, Villani, Alexandra-Chloé, additional, Bacardit, Jaume, additional, Jones, Phil, additional, O’Toole, Edel A., additional, Ogg, Graham S., additional, Rajan, Neil, additional, Reynolds, Nick J., additional, Teichmann, Sarah A., additional, Watt, Fiona, additional, and Haniffa, Muzlifah, additional

Published
2020
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24. Human Developmental Cell Atlas: milestones achieved and the roadmap ahead

Author

Haniffa, Muzlifah, primary, Taylor, Deanne, additional, Linnarsson, Sten, additional, Aronow, Bruce, additional, Bader, Gary, additional, Camara, Pablo, additional, Camp, J. Gray, additional, Chédotal, Alain, additional, Copp, Andrew, additional, Etchevers, Heather, additional, Giacobini, Paolo, additional, Gottgens, Berthold, additional, Guo, Guoji, additional, Hupalowska, Anna, additional, James, Kylie, additional, Kirby, Emily, additional, Kriegstein, Arnold, additional, Lundeberg, Joakim, additional, Marioni, John, additional, Meyer, Kerstin, additional, Niakan, Kathy, additional, Nilsson, Mats, additional, Olabi, Bayanne, additional, Pe'er, Dana, additional, Regev, Aviv, additional, Rood, Jennifer, additional, Rozenblatt-Rosen, Orit, additional, Satija, Rahul, additional, Teichmann, Sarah, additional, Treutlein, Barbara, additional, Vento-Tormo, Roser, additional, and Webb, Simone, additional

Published
2020
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26. A cell atlas of human thymic development defines T cell repertoire formation

Author

Park, Jong-Eun, primary, Botting, Rachel A., additional, Domínguez Conde, Cecilia, additional, Popescu, Dorin-Mirel, additional, Lavaert, Marieke, additional, Kunz, Daniel J., additional, Goh, Issac, additional, Stephenson, Emily, additional, Ragazzini, Roberta, additional, Tuck, Elizabeth, additional, Wilbrey-Clark, Anna, additional, Roberts, Kenny, additional, Kedlian, Veronika R., additional, Ferdinand, John R., additional, He, Xiaoling, additional, Webb, Simone, additional, Maunder, Daniel, additional, Vandamme, Niels, additional, Mahbubani, Krishnaa T., additional, Polanski, Krzysztof, additional, Mamanova, Lira, additional, Bolt, Liam, additional, Crossland, David, additional, de Rita, Fabrizio, additional, Fuller, Andrew, additional, Filby, Andrew, additional, Reynolds, Gary, additional, Dixon, David, additional, Saeb-Parsy, Kourosh, additional, Lisgo, Steven, additional, Henderson, Deborah, additional, Vento-Tormo, Roser, additional, Bayraktar, Omer A., additional, Barker, Roger A., additional, Meyer, Kerstin B., additional, Saeys, Yvan, additional, Bonfanti, Paola, additional, Behjati, Sam, additional, Clatworthy, Menna R., additional, Taghon, Tom, additional, Haniffa, Muzlifah, additional, and Teichmann, Sarah A., additional

Published
2020
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30. PHILOSOPHY AS A FEMINIST SPIRITUALITY AND CRITICAL PRACTICE FOR MARY ASTELL.

Author

Webb, Simone

Subjects
*FEMINIST theory, *SPIRITUALITY, *MODERN philosophy, *SOCIAL structure, *PHILOSOPHERS, *SELF, *FEMINIST ethics
Abstract

The question of how gender might inflect and affect philosophy as a way of life has been somewhat neglected, as has the role of philosophical modes of living for historical female philosophers. This essay draws on Michel Foucault's multifaceted, Hadot‐inspired conception of philosophy to show how transformative philosophical practices of the self function as feminist praxis in the work of the early modern feminist philosopher Mary Astell. Philosophy in Astell's texts, the essay argues, is a spiritual practice of the self that at the same time functions as a feminist critique both of sexist social structures and of the self that undertakes the practice. It facilitates women in achieving internal freedom. Finally, the essay discusses potential feminist concerns about Astell's proposed philosophical way of living, before suggesting that it may have value for women today. [ABSTRACT FROM AUTHOR]

Published
2020
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31. The psychology of temper tantrums

Author

Webb, Simone

Subjects
Psychology -- Analysis, Anger in children -- Analysis, Food and beverage industries, Health
Abstract

Temper tantrums are common in the animal kingdom, and are employed to obtain resources from parents. Tantrums are reinforced if parents respond by providing resources. This is true even if the parent does not respond every time, since the child can always hope that the parent may respong in the desired way. Parents should never reward children when they are having a tantrum. Tantrums are normal, and they eventually disappear if parents can resist rewarding them.

Published
1995

32. Dyspraxia: a real problem

Author

Webb, Simone

Subjects
Child development -- Analysis, Motor ability -- Analysis, Food and beverage industries, Health
Abstract

Dyspraxia is a condition affecting the co-ordination of children which can affect up to 10% of children. The children may become isolated due to being unable to carry out a number of tasks such as writing clearly, catching a ball, and eating without dropping food on themselves. The problem is physical and is not related to intelligence. Children can be helped through physiotherapy. The cause of the condition is unknown, though it could be related to anoxia at birth in some cases.

Published
1995

34. A cell atlas of human thymic development defines T cell repertoire formation.

Author

Jong-Eun Park, Botting, Rachel A., Domínguez Conde, Cecilia, Popescu, Dorin-Mirel, Lavaert, Marieke, Kunz, Daniel J., Goh, Issac, Stephenson, Emily, Ragazzini, Roberta, Tuck, Elizabeth, Wilbrey-Clark, Anna, Roberts, Kenny, Kedlian, Veronika R., Ferdinand, John R., Xiaoling He, Webb, Simone, Maunder, Daniel, Vandamme, Niels, Mahbubani, Krishnaa T., and Polanski, Krzysztof

Published
2020
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35. Decoding human fetal liver haematopoiesis

Author

Popescu, Dorin-Mirel, Botting, Rachel A, Stephenson, Emily, Green, Kile, Webb, Simone, Jardine, Laura, Calderbank, Emily F, Polanski, Krzysztof, Goh, Issac, Efremova, Mirjana, Acres, Meghan, Maunder, Daniel, Vegh, Peter, Gitton, Yorick, Park, Jong-Eun, Vento-Tormo, Roser, Miao, Zhichao, Dixon, David, Rowell, Rachel, McDonald, David, Fletcher, James, Poyner, Elizabeth, Reynolds, Gary, Mather, Michael, Moldovan, Corina, Mamanova, Lira, Greig, Frankie, Young, Matthew D, Meyer, Kerstin B, Lisgo, Steven, Bacardit, Jaume, Fuller, Andrew, Millar, Ben, Innes, Barbara, Lindsay, Susan, Stubbington, Michael JT, Kowalczyk, Monika S, Li, Bo, Ashenberg, Orr, Tabaka, Marcin, Dionne, Danielle, Tickle, Timothy L, Slyper, Michal, Rozenblatt-Rosen, Orit, Filby, Andrew, Carey, Peter, Villani, Alexandra-Chloé, Roy, Anindita, Regev, Aviv, Chédotal, Alain, Roberts, Irene, Göttgens, Berthold, Behjati, Sam, Laurenti, Elisa, Teichmann, Sarah A, and Haniffa, Muzlifah

Subjects
Blood Cells, Lymphoid Tissue, Gene Expression Profiling, Stem Cells, Flow Cytometry, 3. Good health, Hematopoiesis, Fetus, Cellular Microenvironment, Liver, embryonic structures, Humans, Female, Single-Cell Analysis
Abstract

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs., We acknowledge funding from the Wellcome Human Cell Atlas Strategic Science Support (WT211276/Z/18/Z); M.H. is funded by Wellcome (WT107931/Z/15/Z), The Lister Institute for Preventive Medicine and NIHR and Newcastle-Biomedical Research Centre; S.A.T. is funded by Wellcome (WT206194), ERC Consolidator and EU MRG-Grammar awards and; S.B. is funded by Wellcome (WT110104/Z/15/Z) and St. Baldrick’s Foundation; E.L. is funded by a Wellcome Sir Henry Dale and Royal Society Fellowships, European Haematology Association, Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and BBSRC.

36. YOUR SHOUT.

Author

WILDING, KYLIE, NICOL-RANN, ANN-MARIE, MACKIE, S., WEBB, SIMONE, and BOLTON, COLLETTE

Abstract

Several letters to the editor and replies are presented in response to articles including one on dating site profiles by Donna McPhail, another one on an issue about biphobia and "Why Do You Have To Be A Hearbreaker?" that were all published in the April 2012 issue.

Published
2012

37. Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia

Author

Eleonora Khabirova, Laura Jardine, Tim H. H. Coorens, Simone Webb, Taryn D. Treger, Justin Engelbert, Tarryn Porter, Elena Prigmore, Grace Collord, Alice Piapi, Sarah A. Teichmann, Sarah Inglott, Owen Williams, Olaf Heidenreich, Matthew D. Young, Karin Straathof, Simon Bomken, Jack Bartram, Muzlifah Haniffa, Sam Behjati, Khabirova, Eleonora [0000-0002-5891-6789], Jardine, Laura [0000-0003-4495-8205], Coorens, Tim HH [0000-0002-5826-3554], Webb, Simone [0000-0003-3058-8952], Prigmore, Elena [0000-0001-8870-0316], Piapi, Alice [0000-0001-8251-3309], Teichmann, Sarah [0000-0002-6294-6366], Williams, Owen [0000-0002-1760-6880], Heidenreich, Olaf [0000-0001-5404-6483], Young, Matthew D [0000-0003-0937-5290], Bomken, Simon [0000-0001-9163-5738], Bartram, Jack [0000-0003-1573-2506], Haniffa, Muzlifah [0000-0002-3927-2084], Behjati, Sam [0000-0002-6600-7665], Apollo - University of Cambridge Repository, and Teichmann, Sarah A [0000-0002-6294-6366]

Subjects
Gene Rearrangement, article, Infant, General Medicine, 631/67/69, Precursor Cell Lymphoblastic Leukemia-Lymphoma, General Biochemistry, Genetics and Molecular Biology, 631/67/1990/283, Bone Marrow, Mutation, Humans, Child, Transcriptome, Myeloid-Lymphoid Leukemia Protein
Abstract

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255, Funder: Newcastle NIHR-Biomedical Research Centre, KMT2A-rearranged infant ALL is an aggressive childhood leukemia with poor prognosis. Here, we investigated the developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia (B-ALL) using bulk messenger RNA (mRNA) meta-analysis and examination of single lymphoblast transcriptomes against a developing bone marrow reference. KMT2A-rearranged infant B-ALL was uniquely dominated by an early lymphocyte precursor (ELP) state, whereas less adverse NUTM1-rearranged infant ALL demonstrated signals of later developing B cells, in line with most other childhood B-ALLs. We compared infant lymphoblasts with ELP cells and revealed that the cancer harbored hybrid myeloid-lymphoid features, including nonphysiological antigen combinations potentially targetable to achieve cancer specificity. We validated surface coexpression of exemplar combinations by flow cytometry. Through analysis of shared mutations in separate leukemias from a child with infant KMT2A-rearranged B-ALL relapsing as AML, we established that KMT2A rearrangement occurred in very early development, before hematopoietic specification, emphasizing that cell of origin cannot be inferred from the transcriptional state.

Published
2022

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