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11 results on '"Polanski, Krzysztof [0000-0002-2586-9576]"'

1. Mapping interindividual dynamics of innate immune response at single-cell resolution

Author

Kumasaka, Natsuhiko, Rostom, Raghd, Huang, Ni, Polanski, Krzysztof, Meyer, Kerstin B, Patel, Sharad, Boyd, Rachel, Gomez, Celine, Barnett, Sam N, Panousis, Nikolaos I, Schwartzentruber, Jeremy, Ghoussaini, Maya, Lyons, Paul A, Calero-Nieto, Fernando J, Göttgens, Berthold, Barnes, Josephine L, Worlock, Kaylee B, Yoshida, Masahiro, Nikolić, Marko Z, Stephenson, Emily, Reynolds, Gary, Haniffa, Muzlifah, Marioni, John C, Stegle, Oliver, Hagai, Tzachi, Teichmann, Sarah A, Kumasaka, Natsuhiko [0000-0002-3557-0375], Polanski, Krzysztof [0000-0002-2586-9576], Meyer, Kerstin B. [0000-0001-5906-1498], Barnett, Sam N. [0000-0002-8968-4319], Ghoussaini, Maya [0000-0002-2415-2143], Lyons, Paul A. [0000-0001-7035-8997], Calero-Nieto, Fernando J. [0000-0003-3358-8253], Göttgens, Berthold [0000-0001-6302-5705], Barnes, Josephine L. [0000-0001-9938-3176], Worlock, Kaylee B. [0000-0002-5656-7634], Yoshida, Masahiro [0000-0002-3521-5322], Nikolić, Marko Z. [0000-0001-6304-6848], Reynolds, Gary [0000-0002-8142-8708], Haniffa, Muzlifah [0000-0002-3927-2084], Marioni, John C. [0000-0001-9092-0852], Stegle, Oliver [0000-0002-8818-7193], Hagai, Tzachi [0000-0002-4575-6624], Teichmann, Sarah A. [0000-0002-6294-6366], Apollo - University of Cambridge Repository, Meyer, Kerstin B [0000-0001-5906-1498], Barnett, Sam N [0000-0002-8968-4319], Lyons, Paul A [0000-0001-7035-8997], Calero-Nieto, Fernando J [0000-0003-3358-8253], Barnes, Josephine L [0000-0001-9938-3176], Worlock, Kaylee B [0000-0002-5656-7634], Nikolić, Marko Z [0000-0001-6304-6848], Marioni, John C [0000-0001-9092-0852], and Teichmann, Sarah A [0000-0002-6294-6366]

Subjects
Humans, COVID-19, Pentaerythritol Tetranitrate, Immunity, Innate, Genome-Wide Association Study, Autoimmune Diseases
Abstract

Common genetic variants across individuals modulate the cellular response to pathogens and are implicated in diverse immune pathologies, yet how they dynamically alter the response upon infection is not well understood. Here, we triggered antiviral responses in human fibroblasts from 68 healthy donors, and profiled tens of thousands of cells using single-cell RNA-sequencing. We developed GASPACHO (GAuSsian Processes for Association mapping leveraging Cell HeterOgeneity), a statistical approach designed to identify nonlinear dynamic genetic effects across transcriptional trajectories of cells. This approach identified 1,275 expression quantitative trait loci (local false discovery rate 10%) that manifested during the responses, many of which were colocalized with susceptibility loci identified by genome-wide association studies of infectious and autoimmune diseases, including the OAS1 splicing quantitative trait locus in a COVID-19 susceptibility locus. In summary, our analytical approach provides a unique framework for delineation of the genetic variants that shape a wide spectrum of transcriptional responses at single-cell resolution.

Published
2023

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

Author

Madissoon, Elo, Oliver, Amanda J, Kleshchevnikov, Vitalii, Wilbrey-Clark, Anna, Polanski, Krzysztof, Richoz, Nathan, Ribeiro Orsi, Ana, Mamanova, Lira, Bolt, Liam, Elmentaite, Rasa, Pett, J Patrick, Huang, Ni, Xu, Chuan, He, Peng, Dabrowska, Monika, Pritchard, Sophie, Tuck, Liz, Prigmore, Elena, Perera, Shani, Knights, Andrew, Oszlanczi, Agnes, Hunter, Adam, Vieira, Sara F, Patel, Minal, Lindeboom, Rik GH, Campos, Lia S, Matsuo, Kazuhiko, Nakayama, Takashi, Yoshida, Masahiro, Worlock, Kaylee B, Nikolić, Marko Z, Georgakopoulos, Nikitas, Mahbubani, Krishnaa T, Saeb-Parsy, Kourosh, Bayraktar, Omer Ali, Clatworthy, Menna R, Stegle, Oliver, Kumasaka, Natsuhiko, Teichmann, Sarah A, Meyer, Kerstin B, Oliver, Amanda J [0000-0003-1690-9027], Polanski, Krzysztof [0000-0002-2586-9576], Ribeiro Orsi, Ana [0000-0002-4939-1423], Mamanova, Lira [0000-0003-1463-8622], Elmentaite, Rasa [0000-0001-7366-5466], Pett, J Patrick [0000-0002-5249-444X], He, Peng [0000-0002-2457-3554], Tuck, Liz [0000-0002-1837-7549], Prigmore, Elena [0000-0001-8870-0316], Vieira, Sara F [0000-0002-1021-3021], Lindeboom, Rik GH [0000-0002-3660-504X], Nakayama, Takashi [0000-0002-8493-899X], Yoshida, Masahiro [0000-0002-3521-5322], Worlock, Kaylee B [0000-0002-5656-7634], Nikolić, Marko Z [0000-0001-6304-6848], Georgakopoulos, Nikitas [0000-0002-1879-6583], Mahbubani, Krishnaa T [0000-0002-1327-2334], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Bayraktar, Omer Ali [0000-0001-6055-277X], Kumasaka, Natsuhiko [0000-0002-3557-0375], Teichmann, Sarah A [0000-0002-6294-6366], Meyer, Kerstin B [0000-0001-5906-1498], and Apollo - University of Cambridge Repository

Subjects
B-Lymphocytes, 631/250, Genetics, article, Humans, Epithelial Cells, 631/443, Respiratory Mucosa, 631/80, 692/699/1785, Lung, 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 atlungcellatlas.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

3. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

Author

Elena Prigmore, Louis-François Handfield, Michael R. Stratton, Tong Li, Mercedes Jimenez-Linan, Lucy Gardner, Luz Garcia-Alonso, Tarryn Porter, Krishnaa T. Mahbubani, Vitalii Kleshchevnikov, Anna Arutyunyan, Hassan Massalha, Monika Dabrowska, Paul Ayuk, Kwasi Kwakwa, Ashley Moffett, Benjamin Woodhams, Kourosh Saeb-Parsy, Ridma C. Fernando, Regina Hoo, Elizabeth Tuck, Konstantina Nikolakopoulou, Stijn van Dongen, Valentina Lorenzi, Jong-Eun Park, Kenny Roberts, Cecilia Icoresi Mazzeo, Margherita Y. Turco, Vasyl Vaskivskyi, Martin Prete, Aleksandra Tarkowska, Roser Vento-Tormo, Krzysztof Polanski, Carmen Sancho-Serra, Cecilia Lindskog, Omer Ali Bayraktar, Vladimir Yu. Kiselev, Sarah A. Teichmann, Lia S. Campos, Luiza Moore, Roberts, Kenny [0000-0001-6155-0821], Nikolakopoulou, Konstantina [0000-0003-2306-590X], Woodhams, Benjamin [0000-0003-2801-5733], Arutyunyan, Anna [0000-0003-0453-5443], Polanski, Krzysztof [0000-0002-2586-9576], Li, Tong [0000-0002-8240-4476], Vaskivskyi, Vasyl [0000-0002-4080-4965], Mahbubani, Krishnaa T. [0000-0002-1327-2334], Stratton, Michael R. [0000-0001-6035-153X], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Moffett, Ashley [0000-0002-8388-9073], Moore, Luiza [0000-0001-5315-516X], Bayraktar, Omer A. [0000-0001-6055-277X], Teichmann, Sarah A. [0000-0002-6294-6366], Vento-Tormo, Roser [0000-0002-9870-8474], Apollo - University of Cambridge Repository, Mahbubani, Krishnaa T [0000-0002-1327-2334], Stratton, Michael R [0000-0001-6035-153X], Bayraktar, Omer A [0000-0001-6055-277X], Teichmann, Sarah A [0000-0002-6294-6366], Mahbubani, Krishnaa [0000-0002-1327-2334], and Teichmann, Sarah [0000-0002-6294-6366]

Subjects
631/45, Cell type, Notch signaling pathway, Reproduktionsmedicin och gynekologi, In Vitro Techniques, Cell fate determination, Biology, Endometrium, Tissue Culture Techniques, Transcriptome, Spatio-Temporal Analysis, Downregulation and upregulation, Obstetrics, Gynecology and Reproductive Medicine, Genetics, Organoid, medicine, Humans, Cell Lineage, Gonadal Steroid Hormones, Menstrual Cycle, Receptors, Notch, Uterus, article, Wnt signaling pathway, Cell Differentiation, Endometrial Neoplasms, Cell biology, Organoids, Wnt Proteins, medicine.anatomical_structure, Cellular Microenvironment, Female, 631/80, Signal Transduction
Abstract

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma. Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively. Correction in: Nature Genetics, 55, page 165 (2023)DOI: 10.1038/s41588-022-01287-6

Published
2021

4. Mapping the developing human immune system across organs

Author

Suo, Chenqu, Dann, Emma, Goh, Issac, Jardine, Laura, Kleshchevnikov, Vitalii, Park, Jong-Eun, Botting, Rachel A, Stephenson, Emily, Engelbert, Justin, Tuong, Zewen Kelvin, Polanski, Krzysztof, Yayon, Nadav, Xu, Chuan, Suchanek, Ondrej, Elmentaite, Rasa, Domínguez Conde, Cecilia, He, Peng, Pritchard, Sophie, Miah, Mohi, Moldovan, Corina, Steemers, Alexander S, Mazin, Pavel, Prete, Martin, Horsfall, Dave, Marioni, John C, Clatworthy, Menna R, Haniffa, Muzlifah, Teichmann, Sarah A, Suo, Chenqu [0000-0002-8813-0875], Dann, Emma [0000-0002-7400-7438], Goh, Issac [0000-0002-6397-3518], Jardine, Laura [0000-0003-4495-8205], Kleshchevnikov, Vitalii [0000-0001-9110-7441], Park, Jong-Eun [0000-0002-1687-2423], Botting, Rachel A [0000-0001-9595-4605], Stephenson, Emily [0000-0002-4244-4019], Tuong, Zewen Kelvin [0000-0002-6735-6808], Polanski, Krzysztof [0000-0002-2586-9576], Yayon, Nadav [0000-0002-7034-0524], Xu, Chuan [0000-0002-6265-999X], Suchanek, Ondrej [0000-0003-1048-5251], Elmentaite, Rasa [0000-0001-7366-5466], Domínguez Conde, Cecilia [0000-0002-8684-4655], He, Peng [0000-0002-2457-3554], Moldovan, Corina [0000-0001-5021-6473], Steemers, Alexander S [0000-0002-7162-7279], Mazin, Pavel [0000-0001-9268-3352], Prete, Martin [0000-0002-5946-821X], Horsfall, Dave [0000-0002-8086-812X], Marioni, John C [0000-0001-9092-0852], Clatworthy, Menna R [0000-0002-3340-9828], Haniffa, Muzlifah [0000-0002-3927-2084], Teichmann, Sarah A [0000-0002-6294-6366], and Apollo - University of Cambridge Repository

Subjects
Multidisciplinary, Organ Specificity, Immune System, Humans, Genomics, Lymphocytes, RNA-Seq, Single-Cell Analysis, Monocytes
Abstract

Single-cell genomics studies have decoded the immune cell composition of several human prenatal organs but were limited in describing the developing immune system as a distributed network across tissues. We profiled nine prenatal tissues combining single-cell RNA sequencing, antigen-receptor sequencing, and spatial transcriptomics to reconstruct the developing human immune system. This revealed the late acquisition of immune-effector functions by myeloid and lymphoid cell subsets and the maturation of monocytes and T cells before peripheral tissue seeding. Moreover, we uncovered system-wide blood and immune cell development beyond primary hematopoietic organs, characterized human prenatal B1 cells, and shed light on the origin of unconventional T cells. Our atlas provides both valuable data resources and biological insights that will facilitate cell engineering, regenerative medicine, and disease understanding.

Published
2022

5. Local and systemic responses to SARS-CoV-2 infection in children and adults

Author

Gottgens, Berthold, Yoshida, Masahiro, Worlock, Kaylee, Yoshida, Masahiro [0000-0002-3521-5322], Worlock, Kaylee B [0000-0002-5656-7634], Lindeboom, Rik GH [0000-0002-3660-504X], Kumasaka, Natsuhiko [0000-0002-3557-0375], Dominguez Conde, Cecilia [0000-0002-8684-4655], Mamanova, Lira [0000-0003-1463-8622], Bolt, Liam [0000-0001-7293-0774], Richardson, Laura [0000-0002-8075-3816], Polanski, Krzysztof [0000-0002-2586-9576], Barnes, Josephine L [0000-0001-9938-3176], Allen-Hyttinen, Jessica [0000-0003-4644-0362], Jones, Brendan C [0000-0002-2637-8859], Sungnak, Waradon [0000-0002-0136-4960], Pett, J Patrick [0000-0002-5249-444X], Weller, Juliane [0000-0002-1310-6168], Prigmore, Elena [0000-0001-8870-0316], Chu, Vivian [0000-0003-1376-1186], Cohen, Jonathan M [0000-0003-1004-5598], Cane, Clare [0000-0002-3545-768X], Shibuya, Soichi [0000-0002-4274-1312], Herczeg, Iván T [0000-0003-1281-3634], Wunderink, Richard G [0000-0002-8527-4195], Gao, Catherine A [0000-0001-5576-3943], Reynolds, Gary [0000-0002-8142-8708], Haniffa, Muzlifah [0000-0002-3927-2084], Bowyer, Georgina S [0000-0002-2058-4045], Calero-Nieto, Fernando J [0000-0003-3358-8253], Göttgens, Berthold [0000-0001-6302-5705], Jolly, Clare [0000-0002-4603-2281], De Coppi, Paolo [0000-0002-1659-0207], Smith, Claire M [0000-0002-8913-0009], Misharin, Alexander V [0000-0003-2879-3789], Janes, Sam M [0000-0002-6634-5939], Teichmann, Sarah A [0000-0002-6294-6366], Nikolić, Marko Z [0000-0001-6304-6848], Meyer, Kerstin B [0000-0001-5906-1498], and Apollo - University of Cambridge Repository

Subjects
Cambridge Stem Cell Institute
Abstract

It is not fully understood why COVID-19 is typically milder in children To examine differences in response to SARS-CoV-2 infection in children and adults, we analysed paediatric and adult COVID-19 patients and healthy controls (total n=93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In healthy paediatric airways, we observed cells already in an interferon-activated state, that upon SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon-responses restrict viral replication and disease progression. The systemic response in children was characterised by increases in naive lymphocytes and a depletion of natural killer cells, while in adults cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signaling in early infection, and identify novel epithelial cell states that associate with COVID-19 and age. Our matching nasal and blood data showed a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were massively reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

Published
2022

6. Cells of the adult human heart

Author

Litviňuková, Monika, Talavera-López, Carlos, Maatz, Henrike, Reichart, Daniel, Worth, Catherine L., Lindberg, Eric L., Kanda, Masatoshi, Polanski, Krzysztof, Heinig, Matthias, Lee, Michael, Nadelmann, Emily R., Roberts, Kenny, Tuck, Liz, Fasouli, Eirini S., DeLaughter, Daniel M., McDonough, Barbara, Wakimoto, Hiroko, Gorham, Joshua M., Samari, Sara, Mahbubani, Krishnaa T., Saeb-Parsy, Kourosh, Patone, Giannino, Boyle, Joseph J., Zhang, Hongbo, Zhang, Hao, Viveiros, Anissa, Oudit, Gavin Y., Bayraktar, Omer Ali, Seidman, J. G., Seidman, Christine E., Noseda, Michela, Hubner, Norbert, Teichmann, Sarah A., Worth, Catherine L. [0000-0002-1796-9606], Kanda, Masatoshi [0000-0003-3468-3586], Polanski, Krzysztof [0000-0002-2586-9576], Heinig, Matthias [0000-0002-5612-1720], Lee, Michael [0000-0002-0186-4439], Roberts, Kenny [0000-0001-6155-0821], Wakimoto, Hiroko [0000-0003-0225-6424], Mahbubani, Krishnaa T. [0000-0002-1327-2334], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Patone, Giannino [0000-0002-7242-0341], Boyle, Joseph J. [0000-0002-4337-3320], Bayraktar, Omer Ali [0000-0001-6055-277X], Seidman, Christine E. [0000-0001-6380-1209], Noseda, Michela [0000-0002-9553-5029], Hubner, Norbert [0000-0002-1218-6223], Teichmann, Sarah A. [0000-0002-6294-6366], Apollo - University of Cambridge Repository, Worth, Catherine L [0000-0002-1796-9606], Mahbubani, Krishnaa T [0000-0002-1327-2334], Boyle, Joseph J [0000-0002-4337-3320], Seidman, Christine E [0000-0001-6380-1209], Teichmann, Sarah A [0000-0002-6294-6366], and British Heart Foundation

Subjects
Male, PROTEIN, 13, Epithelium, Heart development, ENRICHMENT ANALYSIS, Genetics research, Adipocytes, Homeostasis, Myocytes, Cardiac, RNA-SEQ, Neurons, Multidisciplinary, SMOOTH-MUSCLE, Research Highlight, Multidisciplinary Sciences, ADIPOSE-TISSUE, Science & Technology - Other Topics, Female, Angiotensin-Converting Enzyme 2, Single-Cell Analysis, EXPRESSION, Adult, GROWTH-FACTOR, General Science & Technology, 45/62, Heart Ventricles, Article, 38/91, 14/32, Humans, Heart Atria, Muscle, Skeletal, RESIDENT CARDIAC MACROPHAGES, Science & Technology, SARS-CoV-2, Gene Expression Profiling, Macrophages, Myocardium, 692/308/2056, Epithelial Cells, Fibroblasts, ENDOTHELIAL-CELLS, GENE, 631/208/199, Cardiovascular and Metabolic Diseases, MYOCARDIAL INJURY, Gene expression, Stromal Cells, Pericytes, Transcriptome, Genome-Wide Association Study, Receptors, Coronavirus
Abstract

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies., Single-cell and single-nucleus RNA sequencing are used to construct a cellular atlas of the human heart that will aid further research into cardiac physiology and disease.

Published
2020

7. Cells of the human intestinal tract mapped across space and time

Author

Cecilia Domínguez Conde, Ni Huang, Omer Ali Bayraktar, Krishnaa T. Mahbubani, Holm H. Uhlig, Justin Engelbert, Steven Leonard, Emma Dann, Minal Patel, Aaron M. Fleming, Sara F. Vieira, C. Elizabeth Hook, Sarah A. Teichmann, Lia S. Campos, Emily Stephenson, Issac Goh Kai’En, Sophie Pritchard, Stijn van Dongen, Michael D Morgan, Kourosh Saeb-Parsy, Krzysztof Polanski, Rasa Elmentaite, Kenny Roberts, John C. Marioni, Thomas R. W. Oliver, Natsuhiko Kumasaka, Matthias Zilbauer, Roger A. Barker, Francesca Perrone, Kylie R. James, Kerstin B Meyer, Muzlifah Haniffa, Komal Nayak, Menna R. Clatworthy, Vitalii Kleshchevnikov, Steven Lisgo, Liam Bolt, Lira Mamanova, Xiaoling He, Monika Dabrowska, Rachel A. Botting, Matilda Katan, Hamish W King, Elmentaite, Rasa [0000-0001-7366-5466], Kumasaka, Natsuhiko [0000-0002-3557-0375], Roberts, Kenny [0000-0001-6155-0821], Dann, Emma [0000-0002-7400-7438], King, Hamish W. [0000-0001-5972-8926], Bolt, Liam [0000-0001-7293-0774], Vieira, Sara F. [0000-0002-1021-3021], Mamanova, Lira [0000-0003-1463-8622], Katan, Matilda [0000-0001-9992-8375], Oliver, Thomas R. W. [0000-0003-4306-0102], Domínguez Conde, Cecilia [0000-0002-8684-4655], Botting, Rachel A. [0000-0001-9595-4605], Polanski, Krzysztof [0000-0002-2586-9576], Morgan, Michael D. [0000-0003-0757-0711], Marioni, John C. [0000-0001-9092-0852], Bayraktar, Omer Ali [0000-0001-6055-277X], Meyer, Kerstin B. [0000-0001-5906-1498], Uhlig, Holm H. [0000-0002-6111-7355], Mahbubani, Krishnaa T. [0000-0002-1327-2334], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Zilbauer, Matthias [0000-0002-7272-0547], Haniffa, Muzlifah [0000-0002-3927-2084], James, Kylie R. [0000-0002-7107-0650], Teichmann, Sarah A. [0000-0002-6294-6366], Apollo - University of Cambridge Repository, King, Hamish W [0000-0001-5972-8926], Vieira, Sara F [0000-0002-1021-3021], Oliver, Thomas RW [0000-0003-4306-0102], Botting, Rachel A [0000-0001-9595-4605], Morgan, Michael D [0000-0003-0757-0711], Marioni, John C [0000-0001-9092-0852], Meyer, Kerstin B [0000-0001-5906-1498], Uhlig, Holm H [0000-0002-6111-7355], Mahbubani, Krishnaa T [0000-0002-1327-2334], James, Kylie R [0000-0002-7107-0650], Teichmann, Sarah A [0000-0002-6294-6366], and Oliver, Thomas R W [0000-0003-4306-0102]

Subjects
Aging, Time Factors, Organogenesis, Cell, Datasets as Topic, Inflammatory bowel disease, 14, Enteric Nervous System, Mice, Crohn Disease, Child, 631/114/2391, health care economics and organizations, Crohn's disease, Multidisciplinary, article, humanities, Cell biology, Intestines, medicine.anatomical_structure, Health, Female, 38/39, medicine.symptom, 631/136, Signal Transduction, Adult, Cellular signalling networks, education, Inflammation, Biology, 38/91, 14/32, Immune system, Fetus, Spatio-Temporal Analysis, 692/699/1503/257/1402, Developmental biology, medicine, Animals, Humans, 45, Receptors, IgG, Epithelial Cells, medicine.disease, Embryonic stem cell, Gastrointestinal Microbiome, Mice, Inbred C57BL, Metagenome, Enteric nervous system, Lymph Nodes
Abstract

Funder: Medical Research Council, The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.

Published
2021
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8. 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., Teichmann, Sarah A., Clatworthy, Menna R., Marioni, John C., Göttgens, Berthold, Haniffa, Muzlifah, Baker, Stephen, Bradley, John R., Dougan, Gordon, Goodfellow, Ian G., Gupta, Ravindra K., Hess, Christoph, Kingston, Nathalie, Lehner, Paul J., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Smith, Kenneth G. C., Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, De Sa, Aloka, Epping, Madeline, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Marsden, Jimmy, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Richoz, Nathan, Sharma, Rahul, Turner, Lori, De Bie, Eckart M. D. D., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Michael, Alice, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, Stefano, Giovanni Di, Allison, John, Butcher, Helen, Caputo, Daniela, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Graves, Barbara, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Gresley, Emma Le, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Calero-Nieto, Fernando J. [0000-0003-3358-8253], Morgan, Michael D. [0000-0003-0757-0711], Tuong, Zewen Kelvin [0000-0002-6735-6808], Sungnak, Waradon [0000-0002-0136-4960], Yoshida, Masahiro [0000-0002-3521-5322], Kumasaka, Natsuhiko [0000-0002-3557-0375], Spegarova, Jarmila Stremenova [0000-0002-0710-9266], Wilson, Nicola K. [0000-0003-0865-7333], Mende, Nicole [0000-0002-5078-2333], Gardner, Louis C. S. [0000-0002-7200-978X], Goh, Issac [0000-0002-6397-3518], Horsfall, Dave [0000-0002-8086-812X], Webb, Simone [0000-0003-3058-8952], Mather, Michael W. [0000-0001-7972-7111], Lindeboom, Rik G. H. [0000-0002-3660-504X], Dann, Emma [0000-0002-7400-7438], Polanski, Krzysztof [0000-0002-2586-9576], Payne, Rebecca P. [0000-0002-9037-7367], Baker, Kenneth F. [0000-0002-6735-2911], Schim van der Loeff, Ina C. D. [0000-0003-1196-6196], Barr, Andrew S. [0000-0002-8084-7644], Mescia, Federica [0000-0002-2759-4027], Barnes, Josephine L. [0000-0001-9938-3176], Janes, Sam M. [0000-0002-6634-5939], Smith, Claire M. [0000-0002-8913-0009], Coupland, Paul [0000-0002-2871-3374], Bacardit, Jaume [0000-0002-2692-7205], King, Hamish W. [0000-0001-5972-8926], Rostron, Anthony J. [0000-0002-9336-1723], Simpson, A. John [0000-0003-4731-7294], Hambleton, Sophie [0000-0001-7954-3267], Laurenti, Elisa [0000-0002-9917-9092], Lyons, Paul A. [0000-0001-7035-8997], Meyer, Kerstin B. [0000-0001-5906-1498], Nikolić, Marko Z. [0000-0001-6304-6848], Smith, Kenneth G. C. [0000-0003-3829-4326], Teichmann, Sarah A. [0000-0002-6294-6366], Clatworthy, Menna R. [0000-0002-3340-9828], Marioni, John C. [0000-0001-9092-0852], Göttgens, Berthold [0000-0001-6302-5705], Haniffa, Muzlifah [0000-0002-3927-2084], and Apollo - University of Cambridge Repository

Subjects
692/699/255/2514, 631/208/514/1949, article, 631/250/232, 631/250/254, 631/326/596/4130
Abstract

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255, Funder: University College London, Birkbeck MRC Doctoral Training Programme, Funder: The Jikei University School of Medicine, Funder: Action Medical Research (GN2779), Funder: NIHR Clinical Lectureship (CL-2017-01-004), Funder: NIHR (ACF-2018-01-004) and the BMA Foundation, Funder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194), Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944), Funder: Barbour Foundation, Funder: ERC Consolidator and EU MRG-Grammar awards, Funder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002), Funder: European Molecular Biology Laboratory (EMBL), 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.

Published
2021
Full Text
View/download PDF

9. 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 CS, Goh, Issac, Horsfall, Dave, McGrath, Jim, Webb, Simone, Mather, Michael W, Lindeboom, Rik GH, 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 CD, 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, Cambridge Institute Of Therapeutic Immunology And Infectious Disease-National Institute Of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration, Rostron, Anthony J, Simpson, A John, Hambleton, Sophie, Laurenti, Elisa, Lyons, Paul A, Meyer, Kerstin B, Nikolić, Marko Z, Duncan, Christopher JA, Smith, Kenneth GC, Teichmann, Sarah A, Clatworthy, Menna R, Marioni, John C, Göttgens, Berthold, Haniffa, Muzlifah, Calero-Nieto, Fernando J [0000-0003-3358-8253], Morgan, Michael D [0000-0003-0757-0711], Tuong, Zewen Kelvin [0000-0002-6735-6808], Sungnak, Waradon [0000-0002-0136-4960], Yoshida, Masahiro [0000-0002-3521-5322], Kumasaka, Natsuhiko [0000-0002-3557-0375], Spegarova, Jarmila Stremenova [0000-0002-0710-9266], Wilson, Nicola K [0000-0003-0865-7333], Mende, Nicole [0000-0002-5078-2333], Gardner, Louis CS [0000-0002-7200-978X], Goh, Issac [0000-0002-6397-3518], Horsfall, Dave [0000-0002-8086-812X], Webb, Simone [0000-0003-3058-8952], Mather, Michael W [0000-0001-7972-7111], Lindeboom, Rik GH [0000-0002-3660-504X], Dann, Emma [0000-0002-7400-7438], Polanski, Krzysztof [0000-0002-2586-9576], Payne, Rebecca P [0000-0002-9037-7367], Baker, Kenneth F [0000-0002-6735-2911], Schim van der Loeff, Ina CD [0000-0003-1196-6196], Barr, Andrew S [0000-0002-8084-7644], Mescia, Federica [0000-0002-2759-4027], Barnes, Josephine L [0000-0001-9938-3176], Janes, Sam M [0000-0002-6634-5939], Smith, Claire M [0000-0002-8913-0009], Coupland, Paul [0000-0002-2871-3374], Bacardit, Jaume [0000-0002-2692-7205], King, Hamish W [0000-0001-5972-8926], Rostron, Anthony J [0000-0002-9336-1723], Simpson, A John [0000-0003-4731-7294], Hambleton, Sophie [0000-0001-7954-3267], Laurenti, Elisa [0000-0002-9917-9092], Lyons, Paul A [0000-0001-7035-8997], Meyer, Kerstin B [0000-0001-5906-1498], Nikolić, Marko Z [0000-0001-6304-6848], Smith, Kenneth GC [0000-0003-3829-4326], Teichmann, Sarah A [0000-0002-6294-6366], Clatworthy, Menna R [0000-0002-3340-9828], Marioni, John C [0000-0001-9092-0852], Göttgens, Berthold [0000-0001-6302-5705], Haniffa, Muzlifah [0000-0002-3927-2084], and Apollo - University of Cambridge Repository

Subjects
Cross-Sectional Studies, Proteome, SARS-CoV-2, T-Lymphocytes, Receptors, Antigen, T-Cell, COVID-19, Humans, Receptors, Antigen, B-Cell, Single-Cell Analysis, Transcriptome, Monocytes
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.

Published
2021
Full Text
View/download PDF

10. Tumors induce de novo steroid biosynthesis in T cells to evade immunity

Author

Klaus Okkenhaug, Edward Ryder, Izabela Walczak, Sarah A. Teichmann, Lia S. Campos, Jacqueline D. Shields, Nuno A. Fonseca, Bidesh Mahata, Angela Riedel, David J. Adams, Xi Chen, Jhuma Pramanik, Krzysztof Polanski, Gozde Kar, Louise van der Weyden, Kousik Kundu, Graham Duddy, Mahata, Bidesh [0000-0002-4506-0184], Polanski, Krzysztof [0000-0002-2586-9576], Chen, Xi [0000-0003-2648-3146], Fonseca, Nuno A [0000-0003-4832-578X], Kundu, Kousik [0000-0002-1019-8351], Ryder, Edward [0000-0002-1799-9899], Okkenhaug, Klaus [0000-0002-9432-4051], Adams, David J [0000-0001-9490-0306], Shields, Jacqueline D [0000-0003-2153-9710], Teichmann, Sarah A [0000-0002-6294-6366], Apollo - University of Cambridge Repository, Fonseca, Nuno A. [0000-0003-4832-578X], Adams, David J. [0000-0001-9490-0306], Shields, Jacqueline D. [0000-0003-2153-9710], and Teichmann, Sarah A. [0000-0002-6294-6366]

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, medicine.medical_treatment, animal diseases, Druggability, General Physics and Astronomy, Transcriptome, 13/1, Mice, 0302 clinical medicine, lcsh:Science, Melanoma, Mice, Knockout, 0303 health sciences, Multidisciplinary, article, Immunosuppression, Primary tumor, 3. Good health, Cell biology, 13/31, medicine.anatomical_structure, 030220 oncology & carcinogenesis, 9, 38/77, Tumour immunology, 64/60, Steroids, 631/67/327, Cancer microenvironment, Science, Transgene, T cell, 13/106, chemical and pharmacologic phenomena, Steroid biosynthesis, Biology, General Biochemistry, Genetics and Molecular Biology, 38, 38/91, 03 medical and health sciences, Immune system, 13/21, Immunity, Cell Line, Tumor, medicine, Animals, Humans, Cholesterol Side-Chain Cleavage Enzyme, 030304 developmental biology, Immune Evasion, General Chemistry, biochemical phenomena, metabolism, and nutrition, medicine.disease, 030104 developmental biology, Cell culture, 631/67/580, Cancer cell, Cancer research, bacteria, lcsh:Q
Abstract

Tumors subvert immune cell function to evade immune responses, yet the complex mechanisms driving immune evasion remain poorly understood. Here we show that tumors induce de novo steroidogenesis in T lymphocytes to evade anti-tumor immunity. Using a transgenic steroidogenesis-reporter mouse line we identify and characterize de novo steroidogenic immune cells, defining the global gene expression identity of these steroid-producing immune cells and gene regulatory networks by using single-cell transcriptomics. Genetic ablation of T cell steroidogenesis restricts primary tumor growth and metastatic dissemination in mouse models. Steroidogenic T cells dysregulate anti-tumor immunity, and inhibition of the steroidogenesis pathway is sufficient to restore anti-tumor immunity. This study demonstrates T cell de novo steroidogenesis as a mechanism of anti-tumor immunosuppression and a potential druggable target., Multiple mechanisms of immune evasion exploited by cancer cells have been described. Here, the authors show that genetic inactivation or pharmacological inhibition of tumor-induced Th2-mediated de novo steroidogenesis are sufficient to restore an efficient anti-tumor immune response and restrict tumor growth.

Published
2020

11. Spatiotemporal immune zonation of the human kidney

Author

Dorin-Mirel Popescu, Steven Lisgo, Nathan Richoz, Grace Collord, Anne Y. Warren, James Nicholson, Sarah J. Farndon, Andrew Filby, Roser Vento-Tormo, Marc Bajénoff, Tevita Aho, Gordon L. Frazer, Kevin W. Loudon, Rachel A. Botting, Matthew D. Young, Joy Ursula Lauren Staniforth, Grant D. Stewart, Martin Del Castillo Velasco-Herrera, Benjamin J. Stewart, Stephen Farrell, Nicholas Coleman, Charlotte Guzzo, James N. Armitage, Menna R. Clatworthy, Emily Stephenson, Johanna Burge, Felipe A. Vieira Braga, Muzlifah Haniffa, Imran Mushtaq, Neil J. Sebire, Thomas J. Mitchell, Kile Green, Susan Lindsay, Lira Mamanova, Krzysztof Polanski, Sam Behjati, Alex Cagan, Alexandra M. Riding, Antony C. P. Riddick, John R. Ferdinand, Dyanne Rampling, Sarah A. Teichmann, Mirjana Efremova, Defence Science and Technology Organisation (DSTO), Australian Government, Great Ormond Street Hospital for Children [London] (GOSH), Newcastle University [Newcastle], Institute of Genetic Medicine, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Department of Histopathology & Pediatric Laboratory Medicine, Great Ormond Street Hospital, Institute of Cellular Medicine [Newcastle], Stewart, Benjamin J [0000-0003-4522-0085], Ferdinand, John R [0000-0003-0936-0128], Young, Matthew D [0000-0003-0937-5290], Mitchell, Thomas J [0000-0003-0761-9503], Loudon, Kevin W [0000-0001-9055-6894], Riding, Alexandra M [0000-0002-6915-5671], Staniforth, Joy UL [0000-0003-2817-0098], Vieira Braga, Felipe A [0000-0003-0206-9258], Botting, Rachel A [0000-0001-9595-4605], Stephenson, Emily [0000-0002-4244-4019], Cagan, Alex [0000-0002-7857-4771], Farndon, Sarah J [0000-0001-6024-4267], Polanski, Krzysztof [0000-0002-2586-9576], Del Castillo Velasco-Herrera, Martin [0000-0001-5956-0211], Guzzo, Charlotte [0000-0003-3742-5961], Collord, Grace [0000-0003-1924-4411], Mamanova, Lira [0000-0003-1463-8622], Aho, Tevita [0000-0001-8456-9285], Mushtaq, Imran [0000-0002-7930-0342], Lisgo, Steven [0000-0001-5186-3971], Lindsay, Susan [0000-0003-2980-4582], Stewart, Grant D [0000-0003-3188-9140], Haniffa, Muzlifah [0000-0002-3927-2084], Teichmann, Sarah A [0000-0002-6294-6366], Behjati, Sam [0000-0002-6600-7665], Clatworthy, Menna R [0000-0002-3340-9828], Apollo - University of Cambridge Repository, and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Myeloid, Neutrophils, Transgene, Mice, Transgenic, Biology, Kidney, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Fetus, Single-cell analysis, medicine, Animals, Humans, Myeloid Cells, Lymphocytes, RNA-Seq, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Macrophages, Gene Expression Regulation, Developmental, Epithelial Cells, biochemical phenomena, metabolism, and nutrition, Epithelium, 3. Good health, Cell biology, Mice, Inbred C57BL, medicine.anatomical_structure, Urinary Tract Infections, bacteria, Female, Single-Cell Analysis, 030217 neurology & neurosurgery, Homeostasis
Abstract

Immune landscape of the human kidney Single-cell RNA sequencing has begun to shed light on the full cellular diversity of specific organs. However, these studies rarely examine organ-specific immune cells. Stewart et al. sequenced healthy adult and fetal kidney samples at a single-cell level to define the heterogeneity in epithelial, myeloid, and lymphoid cells. From this dataset, they identified zonation of cells, with relevance to disease and the varied perturbations that occur in different tumor settings. This profiling of the human kidney generates a comprehensive census of existing cell populations that will help inform the diagnosis and treatment of kidney-related diseases. Science , this issue p. 1461

Published
2018

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