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1. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Author

Snyder, Michael P, Lin, Shin, Posgai, Amanda, Atkinson, Mark, Regev, Aviv, Rood, Jennifer, Rozenblatt-Rosen, Orit, Gaffney, Leslie, Hupalowska, Anna, Satija, Rahul, Gehlenborg, Nils, Shendure, Jay, Laskin, Julia, Harbury, Pehr, Nystrom, Nicholas A, Silverstein, Jonathan C, Bar-Joseph, Ziv, Zhang, Kun, Börner, Katy, Lin, Yiing, Conroy, Richard, Procaccini, Dena, Roy, Ananda L, Pillai, Ajay, Brown, Marishka, Galis, Zorina S, Cai, Long, Trapnell, Cole, Jackson, Dana, Nolan, Garry, Greenleaf, William James, Plevritis, Sylvia, Ahadi, Sara, Nevins, Stephanie A, Lee, Hayan, Schuerch, Christian Martijn, Black, Sarah, Venkataraaman, Vishal Gautham, Esplin, Ed, Horning, Aaron, Bahmani, Amir, Sun, Xin, Jain, Sanjay, Hagood, James, Pryhuber, Gloria, Kharchenko, Peter, Bodenmiller, Bernd, Brusko, Todd, Clare-Salzler, Michael, Nick, Harry, Otto, Kevin, Wasserfall, Clive, Jorgensen, Marda, Brusko, Maigan, Maffioletti, Sergio, Caprioli, Richard M, Spraggins, Jeffrey M, Gutierrez, Danielle, Patterson, Nathan Heath, Neumann, Elizabeth K, Harris, Raymond, deCaestecker, Mark, Fogo, Agnes B, van de Plas, Raf, Lau, Ken, Yuan, Guo-Cheng, Zhu, Qian, Dries, Ruben, Yin, Peng, Saka, Sinem K, Kishi, Jocelyn Y, Wang, Yu, Goldaracena, Isabel, Ye, DongHye, Burnum-Johnson, Kristin E, Piehowski, Paul D, Ansong, Charles, Zhu, Ying, Desai, Tushar, Mulye, Jay, Chou, Peter, Nagendran, Monica, Teichmann, Sarah A, Paten, Benedict, Murphy, Robert F, Ma, Jian, Kiselev, Vladimir Yu, Kingsford, Carl, and Ricarte, Allyson

Subjects
Human Genome, Genetics, Networking and Information Technology R&D, Bioengineering, Aging, Atlases as Topic, Biomedical Research, Female, Health, Humans, International Cooperation, Male, Models, Anatomic, Molecular Biology, National Institutes of Health (U.S.), Organ Specificity, Single-Cell Analysis, United States, q-bio.OT, General Science & Technology
Abstract

Transformative technologies are enabling the construction of threedimensional (3D) maps of tissues with unprecedented spatial and molecularresolution. Over the next seven years, the NIH Common Fund Human BiomolecularAtlas Program (HuBMAP) intends to develop a widely accessible framework forcomprehensively mapping the human body at single-cell resolution by supportingtechnology development, data acquisition, and detailed spatial mapping. HuBMAPwill integrate its efforts with other funding agencies, programs, consortia,and the biomedical research community at large towards the shared vision of acomprehensive, accessible 3D molecular and cellular atlas of the human body, inhealth and various disease settings.

Published
2019

2. Single-cell roadmap of human gonadal development

Author

Garcia-Alonso, Luz, Lorenzi, Valentina, Mazzeo, Cecilia Icoresi, Alves-Lopes, João Pedro, Roberts, Kenny, Sancho-Serra, Carmen, Engelbert, Justin, Marečková, Magda, Gruhn, Wolfram H., Botting, Rachel A., Li, Tong, Crespo, Berta, van Dongen, Stijn, Kiselev, Vladimir Yu, Prigmore, Elena, Herbert, Mary, Moffett, Ashley, Chédotal, Alain, Bayraktar, Omer Ali, Surani, Azim, Haniffa, Muzlifah, and Vento-Tormo, Roser

Published
2022
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3. Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses

Author

Rodríguez-Ubreva, Javier, Arutyunyan, Anna, Bonder, Marc Jan, Del Pino-Molina, Lucía, Clark, Stephen J., de la Calle-Fabregat, Carlos, Garcia-Alonso, Luz, Handfield, Louis-François, Ciudad, Laura, Andrés-León, Eduardo, Krueger, Felix, Català-Moll, Francesc, Rodríguez-Cortez, Virginia C., Polanski, Krzysztof, Mamanova, Lira, van Dongen, Stijn, Kiselev, Vladimir Yu., Martínez-Saavedra, María T., Heyn, Holger, Martín, Javier, Warnatz, Klaus, López-Granados, Eduardo, Rodríguez-Gallego, Carlos, Stegle, Oliver, Kelsey, Gavin, Vento-Tormo, Roser, and Ballestar, Esteban

Published
2022
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4. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

Author

Garcia-Alonso, Luz, Handfield, Louis-François, Roberts, Kenny, Nikolakopoulou, Konstantina, Fernando, Ridma C., Gardner, Lucy, Woodhams, Benjamin, Arutyunyan, Anna, Polanski, Krzysztof, Hoo, Regina, Sancho-Serra, Carmen, Li, Tong, Kwakwa, Kwasi, Tuck, Elizabeth, Lorenzi, Valentina, Massalha, Hassan, Prete, Martin, Kleshchevnikov, Vitalii, Tarkowska, Aleksandra, Porter, Tarryn, Mazzeo, Cecilia Icoresi, van Dongen, Stijn, Dabrowska, Monika, Vaskivskyi, Vasyl, Mahbubani, Krishnaa T., Park, Jong-eun, Jimenez-Linan, Mercedes, Campos, Lia, Kiselev, Vladimir Yu., Lindskog, Cecilia, Ayuk, Paul, Prigmore, Elena, Stratton, Michael R., Saeb-Parsy, Kourosh, Moffett, Ashley, Moore, Luiza, Bayraktar, Omer A., Teichmann, Sarah A., Turco, Margherita Y., and Vento-Tormo, Roser

Published
2021
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5. Author Correction: Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

Author

Garcia-Alonso, Luz, Handfield, Louis-François, Roberts, Kenny, Nikolakopoulou, Konstantina, Fernando, Ridma C., Gardner, Lucy, Woodhams, Benjamin, Arutyunyan, Anna, Polanski, Krzysztof, Hoo, Regina, Sancho-Serra, Carmen, Li, Tong, Kwakwa, Kwasi, Tuck, Elizabeth, Lorenzi, Valentina, Massalha, Hassan, Prete, Martin, Kleshchevnikov, Vitalii, Tarkowska, Aleksandra, Porter, Tarryn, Mazzeo, Cecilia Icoresi, van Dongen, Stijn, Dabrowska, Monika, Vaskivskyi, Vasyl, Mahbubani, Krishnaa T., Park, Jong-eun, Jimenez-Linan, Mercedes, Campos, Lia, Kiselev, Vladimir Yu., Lindskog, Cecilia, Ayuk, Paul, Prigmore, Elena, Stratton, Michael R., Saeb-Parsy, Kourosh, Moffett, Ashley, Moore, Luiza, Bayraktar, Omer A., Teichmann, Sarah A., Turco, Margherita Y., and Vento-Tormo, Roser

Published
2023
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9. Author Correction: Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

Author

Garcia-Alonso, Luz, primary, Handfield, Louis-François, additional, Roberts, Kenny, additional, Nikolakopoulou, Konstantina, additional, Fernando, Ridma C., additional, Gardner, Lucy, additional, Woodhams, Benjamin, additional, Arutyunyan, Anna, additional, Polanski, Krzysztof, additional, Hoo, Regina, additional, Sancho-Serra, Carmen, additional, Li, Tong, additional, Kwakwa, Kwasi, additional, Tuck, Elizabeth, additional, Lorenzi, Valentina, additional, Massalha, Hassan, additional, Prete, Martin, additional, Kleshchevnikov, Vitalii, additional, Tarkowska, Aleksandra, additional, Porter, Tarryn, additional, Mazzeo, Cecilia Icoresi, additional, van Dongen, Stijn, additional, Dabrowska, Monika, additional, Vaskivskyi, Vasyl, additional, Mahbubani, Krishnaa T., additional, Park, Jong-eun, additional, Jimenez-Linan, Mercedes, additional, Campos, Lia, additional, Kiselev, Vladimir Yu., additional, Lindskog, Cecilia, additional, Ayuk, Paul, additional, Prigmore, Elena, additional, Stratton, Michael R., additional, Saeb-Parsy, Kourosh, additional, Moffett, Ashley, additional, Moore, Luiza, additional, Bayraktar, Omer A., additional, Teichmann, Sarah A., additional, Turco, Margherita Y., additional, and Vento-Tormo, Roser, additional

Published
2022
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10. 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

12. Single-Cell Atlas of Common Variable Immunodeficiency reveals germinal center-associated epigenetic dysregulation in B cell responses

Author

Rodriguez-Ubreva, Javier, primary, Arutyunyan, Anna, additional, Bonder, Marc Jan, additional, Del Pino-Molina, Lucia, additional, Clark, Stephen, additional, de la Calle-Fabregat, Carlos, additional, Garcia-Alonso, Luz, additional, Handfield, Louis-Francois, additional, Ciudad, Laura, additional, Andres-Leon, Eduardo, additional, Krueger, Felix, additional, Catala-Moll, Francesc, additional, Rodriguez-Cortez, Virginia C, additional, Polanski, Krzysztof, additional, Mamanova, Lira, additional, van Dongen, Stijn, additional, Kiselev, Vladimir Yu, additional, Martinez-Saavedra, Maria T, additional, Heyn, Holger, additional, Martin, Javier, additional, Warnatz, Klaus, additional, Lopez-Granados, Eduardo, additional, Rodriguez-Gallego, Carlos, additional, Stegle, Oliver, additional, Kelsey, Gavin D, additional, Vento-Tormo, Roser, additional, and Ballestar, Esteban, additional

Published
2021
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14. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Author

Lin, Shin, Posgai, Amanda, Atkinson, Mark, Regev, Aviv, Rood, Jennifer, Rozenblatt-Rosen, Orit, Gaffney, Leslie, Hupalowska, Anna, Satija, Rahul, Gehlenborg, Nils, Shendure, Jay, Laskin, Julia, Harbury, Pehr, Nystrom, Nicholas A., Silverstein, Jonathan C., Bar-Joseph, Ziv, Zhang, Kun, Börner, Katy, Lin, Yiing, Conroy, Richard, Procaccini, Dena, Roy, Ananda L., Pillai, Ajay, Brown, Marishka, Galis, Zorina S., Cai, Long, Trapnell, Cole, Jackson, Dana, Snyder, Michael P., Nolan, Garry, Greenleaf, William James, Plevritis, Sylvia, Ahadi, Sara, Nevins, Stephanie A., Lee, Hayan, Schuerch, Christian Martijn, Black, Sarah, Venkataraaman, Vishal Gautham, Esplin, Ed, Horning, Aaron, Bahmani, Amir, Sun, Xin, Jain, Sanjay, Hagood, James, Pryhuber, Gloria, Kharchenko, Peter, Bodenmiller, Bernd, Brusko, Todd, Clare-Salzler, Michael, Nick, Harry, Otto, Kevin, Wasserfall, Clive, Jorgensen, Marda, Brusko, Maigan, Maffioletti, Sergio, Caprioli, Richard M., Spraggins, Jeffrey M., Gutierrez, Danielle, Patterson, Nathan Heath, Neumann, Elizabeth K., Harris, Raymond, deCaestecker, Mark, Fogo, Agnes B., van de Plas, Raf, Lau, Ken, Yuan, Guo-Cheng, Zhu, Qian, Dries, Ruben, Yin, Peng, Saka, Sinem K., Kishi, Jocelyn Y., Wang, Yu, Goldaracena, Isabel, Ye, DongHye, Burnum-Johnson, Kristin E., Piehowski, Paul D., Ansong, Charles, Zhu, Ying, Desai, Tushar, Mulye, Jay, Chou, Peter, Nagendran, Monica, Teichmann, Sarah A., Paten, Benedict, Murphy, Robert F., Ma, Jian, Kiselev, Vladimir Yu., Kingsford, Carl, Ricarte, Allyson, Keays, Maria, Akoju, Sushma A., Ruffalo, Matthew, Vella, Margaret, McCallum, Chuck, Cross, Leonard E., Friedman, Samuel H., Heiland, Randy, Herr, Bruce, Macklin, Paul, Quardokus, Ellen M., Record, Lisel, Sluka, James P., Weber, Griffin M., Blood, Philip D., Ropelewski, Alexander J., Shirey, William E., Scibek, Robin M., Mabee, Paula, Lenhardt, W. Christopher, Robasky, Kimberly, Michailidis, Stavros, Marioni, John, Butler, Andrew, Stuart, Tim, Fisher, Eyal, Ghazanfar, Shila, Eraslan, Gokcen, Biancalani, Tommaso, Vaishnav, Eeshit D., Roy, Ananda, Galis, Zorina, Srinivas, Pothur, Pawlyk, Aaron, Sechi, Salvatore, Wilder, Elizabeth, Anderson, James, and Apollo - University of Cambridge Repository

Subjects
45/91, 82/80, 45, 631/114/2398, Perspective, 631/208/212, 45/23, 38/39
Abstract

Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions.

Published
2019

20. SC3: consensus clustering of single cell RNA-seq data

Author

Kiselev, Vladimir Yu, Kirschner, Kristina, Schaub, Michael T., Andrews, Tallulah, Yiu, Andrew, Chandra, Tamir, Natarajan, Kedar N., Reik, Wolf, Barahona, Mauricio, Green, Anthony R., and Hemberg, Martin

Subjects
natural sciences
Abstract

Single-cell RNA-seq enables the quantitative characterization of cell types based on global transcriptome profiles. We present single-cell consensus clustering (SC3), a user-friendly tool for unsupervised clustering, which achieves high accuracy and robustness by combining multiple clustering solutions through a consensus approach (http://bioconductor.org/packages/SC3). We demonstrate that SC3 is capable of identifying subclones from the transcriptomes of neoplastic cells collected from patients.

Published
2017

22. Lateral dynamics of charged lipids and peripheral proteins in spatially heterogeneous membranes: Comparison of continuous and Monte Carlo approaches.

Author

Kiselev, Vladimir Yu., Leda, Marcin, Lobanov, Alexey I., Marenduzzo, Davide, and Goryachev, Andrew B.

Subjects
*LIPIDS, *PROTEINS, *BIOLOGICAL membranes, *MONTE Carlo method, *ELECTROSTATICS, *NUMERICAL analysis, *POISSON'S equation, *APPROXIMATION theory, *SIMULATION methods & models
Abstract

Biological membranes are complex environments whose physico-chemical properties are of utmost importance for the understanding of many crucial biological processes. Much attention has been given in the literature to the description of membranes along the z-axis perpendicular to the membrane. Here, we instead consider the lateral dynamics of lipids and peripheral proteins due to their electrostatic interaction. Previously, we constructed a Monte Carlo automaton capable of simulating mutual diffusive dynamics of charged lipids and associated positively charged peptides. Here, we derive and numerically analyze a system of Poisson-Boltzmann-Nernst-Planck (PBNP) equations that provide a mean-field approximation compatible with our Monte Carlo model. The thorough comparison between the mean-field PBNP equations and Monte Carlo simulations demonstrates that both the approaches are in a good qualitative agreement in all tested scenarios. We find that the two methods quantitatively deviate when the local charge density is high, presumably because the Poisson-Boltzmann formalism is applicable in the so-called weak coupling limit, whose validity is restricted to low charge densities. Nevertheless, we conclude that the mean-field PBNP approach provides a good approximation for the considerably more detailed Monte Carlo model at only a fraction of the associated computational cost and allows simulation of the membrane lateral dynamics on the space and time scales relevant for the realistic biological problems. [ABSTRACT FROM AUTHOR]

Published
2011
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25. SC3 - consensus clustering of single-cell RNA-Seq data

Author

Kiselev, Vladimir Yu., primary, Kirschner, Kristina, additional, Schaub, Michael T., additional, Andrews, Tallulah, additional, Yiu, Andrew, additional, Chandra, Tamir, additional, Natarajan, Kedar N, additional, Reik, Wolf, additional, Barahona, Mauricio, additional, Green, Anthony R, additional, and Hemberg, Martin, additional

Published
2016
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29. Single-cell roadmap of human gonadal development

Author

Garcia-Alonso, Luz, Lorenzi, Valentina, Mazzeo, Cecilia Icoresi, Alves-Lopes, João Pedro, Roberts, Kenny, Sancho-Serra, Carmen, Engelbert, Justin, Marečková, Magda, Gruhn, Wolfram H, Botting, Rachel A, Li, Tong, Crespo, Berta, Van Dongen, Stijn, Kiselev, Vladimir Yu, Prigmore, Elena, Herbert, Mary, Moffett, Ashley, Chédotal, Alain, Bayraktar, Omer Ali, Surani, Azim, Haniffa, Muzlifah, Vento-Tormo, Roser, Lorenzi, Valentina [0000-0002-3111-4006], Roberts, Kenny [0000-0001-6155-0821], Marečková, Magda [0000-0002-4897-5013], Gruhn, Wolfram H [0000-0001-6072-1916], Botting, Rachel A [0000-0001-9595-4605], Li, Tong [0000-0002-8240-4476], Crespo, Berta [0000-0003-0006-009X], Prigmore, Elena [0000-0001-8870-0316], Moffett, Ashley [0000-0002-8388-9073], Chédotal, Alain [0000-0001-7577-3794], Bayraktar, Omer Ali [0000-0001-6055-277X], Vento-Tormo, Roser [0000-0002-9870-8474], Apollo - University of Cambridge Repository, and Surani, Azim [0000-0002-8640-4318]

Subjects
Male, Sex Differentiation, Immunoglobulins, 45/23, 38/91, 14/32, Mice, PAX8 Transcription Factor, Pregnancy, 631/136/142, Testis, Animals, Humans, Cell Lineage, Receptors, Immunologic, Granulosa Cells, Membrane Glycoproteins, Multidisciplinary, Macrophages, Ovary, article, Membrane Proteins, 45/15, Chromatin, Pregnancy Trimester, First, Germ Cells, Microscopy, Fluorescence, Pregnancy Trimester, Second, Female, 38/39, 64/60, Single-Cell Analysis, 631/80, Transcriptome
Abstract

Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries1. Historically, limited tissue accessibility, a lack of reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal–mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15+ and TREM2+ fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis.

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30. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Author

Lin, Shin, Posgai, Amanda, Atkinson, Mark, Regev, Aviv, Rood, Jennifer, Rozenblatt-Rosen, Orit, Gaffney, Leslie, Hupalowska, Anna, Satija, Rahul, Gehlenborg, Nils, Shendure, Jay, Laskin, Julia, Harbury, Pehr, Nystrom, Nicholas A., Silverstein, Jonathan C., Bar-Joseph, Ziv, Zhang, Kun, Börner, Katy, Lin, Yiing, Conroy, Richard, Procaccini, Dena, Roy, Ananda L., Pillai, Ajay, Brown, Marishka, Galis, Zorina S., Cai, Long, Trapnell, Cole, Jackson, Dana, Snyder, Michael P., Nolan, Garry, Greenleaf, William James, Plevritis, Sylvia, Ahadi, Sara, Nevins, Stephanie A., Lee, Hayan, Schuerch, Christian Martijn, Black, Sarah, Venkataraaman, Vishal Gautham, Esplin, Ed, Horning, Aaron, Bahmani, Amir, Sun, Xin, Jain, Sanjay, Hagood, James, Pryhuber, Gloria, Kharchenko, Peter, Bodenmiller, Bernd, Brusko, Todd, Clare-Salzler, Michael, Nick, Harry, Otto, Kevin, Wasserfall, Clive, Jorgensen, Marda, Brusko, Maigan, Maffioletti, Sergio, Caprioli, Richard M., Spraggins, Jeffrey M., Gutierrez, Danielle, Patterson, Nathan Heath, Neumann, Elizabeth K., Harris, Raymond, DeCaestecker, Mark, Fogo, Agnes B., Van De Plas, Raf, Lau, Ken, Yuan, Guo-Cheng, Zhu, Qian, Dries, Ruben, Yin, Peng, Saka, Sinem K., Kishi, Jocelyn Y., Wang, Yu, Goldaracena, Isabel, Ye, DongHye, Burnum-Johnson, Kristin E., Piehowski, Paul D., Ansong, Charles, Zhu, Ying, Desai, Tushar, Mulye, Jay, Chou, Peter, Nagendran, Monica, Teichmann, Sarah A., Paten, Benedict, Murphy, Robert F., Ma, Jian, Kiselev, Vladimir Yu., Kingsford, Carl, Ricarte, Allyson, Keays, Maria, Akoju, Sushma A., Ruffalo, Matthew, Vella, Margaret, McCallum, Chuck, Cross, Leonard E., Friedman, Samuel H., Heiland, Randy, Herr, Bruce, Macklin, Paul, Quardokus, Ellen M., Record, Lisel, Sluka, James P., Weber, Griffin M., Blood, Philip D., Ropelewski, Alexander J., Shirey, William E., Scibek, Robin M., Mabee, Paula, Lenhardt, W. Christopher, Robasky, Kimberly, Michailidis, Stavros, Marioni, John, Butler, Andrew, Stuart, Tim, Fisher, Eyal, Ghazanfar, Shila, Eraslan, Gokcen, Biancalani, Tommaso, Vaishnav, Eeshit D., Roy, Ananda, Galis, Zorina, Srinivas, Pothur, Pawlyk, Aaron, Sechi, Salvatore, Wilder, Elizabeth, and Anderson, James

Subjects
45/91, 82/80, 45, 631/114/2398, Perspective, 631/208/212, 45/23, 38/39, 3. Good health
Abstract

Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions.

31. Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells

Author

Tomaz Curk, Manuel D. Díaz-Muñoz, Jernej Ule, Vladimir Yu. Kiselev, Nicolas Le Novère, Martin R Turner, Díaz-Muñoz, Manuel D [0000-0002-9227-7474], Kiselev, Vladimir Yu [0000-0003-1893-2255], Le Novère, Nicolas [0000-0002-6309-7327], Curk, Tomaz [0000-0003-4888-7256], Ule, Jernej [0000-0002-2452-4277], Turner, Martin [0000-0002-3801-9896], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, DNA damage, Science, General Physics and Astronomy, RNA-binding protein, Ataxia Telangiectasia Mutated Proteins, Biology, Lymphocyte Activation, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Stress granule, Polysome, P-bodies, Protein biosynthesis, Animals, Humans, RNA, Messenger, lcsh:Science, 3' Untranslated Regions, Etoposide, Messenger RNA, B-Lymphocytes, Multidisciplinary, Three prime untranslated region, General Chemistry, Molecular biology, T-Cell Intracellular Antigen-1, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, Gene Expression Regulation, Protein Biosynthesis, lcsh:Q, Tumor Suppressor Protein p53, 030217 neurology & neurosurgery, DNA Damage
Abstract

Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. Tia1 binds to a subset of transcripts involved in cell stress, including p53 mRNA, and controls translational silencing and RNA granule localization. DNA damage promotes mRNA relocation and translation in part due to dissociation of Tia1 from its mRNA targets. Upon DNA damage, p53 mRNA is released from stress granules and associates with polyribosomes to increase protein synthesis in a CAP-independent manner. Global analysis of cellular mRNA abundance and translation indicates that this is an extended ATM-dependent mechanism to increase protein expression of key modulators of the DNA damage response., Sequestering mRNA in cytoplasmic stress granules is a mechanism for translational repression. Here the authors find that p53 mRNA, present in stress granules in activated B lymphocytes, is released upon DNA damage and is translated in a CAP-independent manner.

Published
2017

32. SC3: consensus clustering of single-cell RNA-seq data.

Author

Kiselev VY, Kirschner K, Schaub MT, Andrews T, Yiu A, Chandra T, Natarajan KN, Reik W, Barahona M, Green AR, and Hemberg M

Subjects
Cluster Analysis, Datasets as Topic, Hematopoietic Stem Cells cytology, Humans, Support Vector Machine, Gene Expression Profiling methods, High-Throughput Nucleotide Sequencing methods, Sequence Analysis, RNA methods, Single-Cell Analysis methods
Abstract

Single-cell RNA-seq enables the quantitative characterization of cell types based on global transcriptome profiles. We present single-cell consensus clustering (SC3), a user-friendly tool for unsupervised clustering, which achieves high accuracy and robustness by combining multiple clustering solutions through a consensus approach (http://bioconductor.org/packages/SC3). We demonstrate that SC3 is capable of identifying subclones from the transcriptomes of neoplastic cells collected from patients.

Published
2017
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