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1,592 results on '"van Oudenaarden, Alexander"'

2. Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress

Author

de Jaime-Soguero, Anchel, Hattemer, Janina, Bufe, Anja, Haas, Alexander, van den Berg, Jeroen, van Batenburg, Vincent, Das, Biswajit, di Marco, Barbara, Androulaki, Stefania, Böhly, Nicolas, Landry, Jonathan J. M., Schoell, Brigitte, Rosa, Viviane S., Villacorta, Laura, Baskan, Yagmur, Trapp, Marleen, Benes, Vladimir, Chabes, Andrei, Shahbazi, Marta, Jauch, Anna, Engel, Ulrike, Patrizi, Annarita, Sotillo, Rocio, van Oudenaarden, Alexander, Bageritz, Josephine, Alfonso, Julieta, Bastians, Holger, and Acebrón, Sergio P.

Published
2024
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5. Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages

Author

Andersson-Rolf, Amanda, Groot, Kelvin, Korving, Jeroen, Begthel, Harry, Hanegraaf, Maaike A.J., VanInsberghe, Michael, Salmén, Fredrik, van den Brink, Stieneke, Lopez-Iglesias, Carmen, Peters, Peter J., Krueger, Daniel, Beumer, Joep, Geurts, Maarten H., Alemany, Anna, Gehart, Helmuth, Carlotti, Françoise, de Koning, Eelco J.P., Chuva de Sousa Lopes, Susana M., van Oudenaarden, Alexander, van Es, Johan H., and Clevers, Hans

Published
2024
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6. Acute multi-level response to defective de novo chromatin assembly in S-phase

Author

Dreyer, Jan, Ricci, Giulia, van den Berg, Jeroen, Bhardwaj, Vivek, Funk, Janina, Armstrong, Claire, van Batenburg, Vincent, Sine, Chance, VanInsberghe, Michael A., Tjeerdsma, Rinskje B., Marsman, Richard, Mandemaker, Imke K., di Sanzo, Simone, Costantini, Juliette, Manzo, Stefano G., Biran, Alva, Burny, Claire, van Vugt, Marcel A.T.M., Völker-Albert, Moritz, Groth, Anja, Spencer, Sabrina L., van Oudenaarden, Alexander, and Mattiroli, Francesca

Published
2024
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8. Functional modules from variable genes: Leveraging percolation to analyze noisy, high-dimensional data

Author

Werner, Steffen, Rozemuller, W Mathijs, Ebbing, Annabel, Alemany, Anna, Traets, Joleen, van Zon, Jeroen S., van Oudenaarden, Alexander, Korswagen, Hendrik C., Stephens, Greg J., and Shimizu, Thomas S.

Subjects
Quantitative Biology - Genomics, Physics - Biological Physics
Abstract

While measurement advances now allow extensive surveys of gene activity (large numbers of genes across many samples), interpretation of these data is often confounded by noise -- expression counts can differ strongly across samples due to variation of both biological and experimental origin. Complimentary to perturbation approaches, we extract functionally related groups of genes by analyzing the standing variation within a sampled population. To distinguish biologically meaningful patterns from uninterpretable noise, we focus on correlated variation and develop a novel density-based clustering approach that takes advantage of a percolation transition generically arising in random, uncorrelated data. We apply our approach to two contrasting RNA sequencing data sets that sample individual variation -- across single cells of fission yeast and whole animals of C. elegans worms -- and demonstrate robust applicability and versatility in revealing correlated gene clusters of diverse biological origin, including cell cycle phase, development/reproduction, tissue-specific functions, and feeding history. Our technique exploits generic features of noisy high-dimensional data and is applicable, beyond gene expression, to feature-rich data that sample population-level variability in the presence of noise., Comment: 13 pages, 8 figures

Published
2020

10. Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development

Author

Sen, Maya, Mooijman, Dylan, Chialastri, Alex, Boisset, Jean-Charles, Popovic, Mina, Heindryckx, Björn, Chuva de Sousa Lopes, Susana M, Dey, Siddharth S, and van Oudenaarden, Alexander

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Genetics, Reproductive Medicine, Pediatric, Human Genome, Stem Cell Research, Stem Cell Research - Embryonic - Non-Human, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Blastocyst, DNA (Cytosine-5-)-Methyltransferase 1, DNA Demethylation, DNA Methylation, Embryonic Development, Embryonic Stem Cells, Female, Humans, Mice, Mice, Knockout, Pregnancy
Abstract

DNA methylation (5mC) is central to cellular identity. The global erasure of 5mC from the parental genomes during preimplantation mammalian development is critical to reset the methylome of gametes to the cells in the blastocyst. While active and passive modes of demethylation have both been suggested to play a role in this process, the relative contribution of these two mechanisms to 5mC erasure remains unclear. Here, we report a single-cell method (scMspJI-seq) that enables strand-specific quantification of 5mC, allowing us to systematically probe the dynamics of global demethylation. When applied to mouse embryonic stem cells, we identified substantial cell-to-cell strand-specific 5mC heterogeneity, with a small group of cells displaying asymmetric levels of 5mCpG between the two DNA strands of a chromosome suggesting loss of maintenance methylation. Next, in preimplantation mouse embryos, we discovered that methylation maintenance is active till the 16-cell stage followed by passive demethylation in a fraction of cells within the early blastocyst at the 32-cell stage of development. Finally, human preimplantation embryos qualitatively show temporally delayed yet similar demethylation dynamics as mouse embryos. Collectively, these results demonstrate that scMspJI-seq is a sensitive and cost-effective method to map the strand-specific genome-wide patterns of 5mC in single cells.

Published
2021

13. Transcription factor induction of vascular blood stem cell niches in vivo

Author

Hagedorn, Elliott J., Perlin, Julie R., Freeman, Rebecca J., Wattrus, Samuel J., Han, Tianxiao, Mao, Clara, Kim, Ji Wook, Fernández-Maestre, Inés, Daily, Madeleine L., D’Amato, Christopher, Fairchild, Michael J., Riquelme, Raquel, Li, Brian, Ragoonanan, Dana A.V.E., Enkhbayar, Khaliun, Henault, Emily L., Wang, Helen G., Redfield, Shelby E., Collins, Samantha H., Lichtig, Asher, Yang, Song, Zhou, Yi, Kunar, Balvir, Gomez-Salinero, Jesus Maria, Dinh, Thanh T., Pan, Junliang, Holler, Karoline, Feldman, Henry A., Butcher, Eugene C., van Oudenaarden, Alexander, Rafii, Shahin, Junker, J. Philipp, and Zon, Leonard I.

Published
2023
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14. High-throughput total RNA sequencing in single cells using VASA-seq

Author

Salmen, Fredrik, De Jonghe, Joachim, Kaminski, Tomasz S., Alemany, Anna, Parada, Guillermo E., Verity-Legg, Joe, Yanagida, Ayaka, Kohler, Timo N., Battich, Nicholas, van den Brekel, Floris, Ellermann, Anna L., Arias, Alfonso Martinez, Nichols, Jennifer, Hemberg, Martin, Hollfelder, Florian, and van Oudenaarden, Alexander

Published
2022
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15. The Human Cell Atlas White Paper

Author

Regev, Aviv, Teichmann, Sarah, Rozenblatt-Rosen, Orit, Stubbington, Michael, Ardlie, Kristin, Amit, Ido, Arlotta, Paola, Bader, Gary, Benoist, Christophe, Biton, Moshe, Bodenmiller, Bernd, Bruneau, Benoit, Campbell, Peter, Carmichael, Mary, Carninci, Piero, Castelo-Soccio, Leslie, Clatworthy, Menna, Clevers, Hans, Conrad, Christian, Eils, Roland, Freeman, Jeremy, Fugger, Lars, Goettgens, Berthold, Graham, Daniel, Greka, Anna, Hacohen, Nir, Haniffa, Muzlifah, Helbig, Ingo, Heuckeroth, Robert, Kathiresan, Sekar, Kim, Seung, Klein, Allon, Knoppers, Bartha, Kriegstein, Arnold, Lander, Eric, Lee, Jane, Lein, Ed, Linnarsson, Sten, Macosko, Evan, MacParland, Sonya, Majovski, Robert, Majumder, Partha, Marioni, John, McGilvray, Ian, Merad, Miriam, Mhlanga, Musa, Naik, Shalin, Nawijn, Martijn, Nolan, Garry, Paten, Benedict, Pe'er, Dana, Philippakis, Anthony, Ponting, Chris, Quake, Steve, Rajagopal, Jayaraj, Rajewsky, Nikolaus, Reik, Wolf, Rood, Jennifer, Saeb-Parsy, Kourosh, Schiller, Herbert, Scott, Steve, Shalek, Alex, Shapiro, Ehud, Shin, Jay, Skeldon, Kenneth, Stratton, Michael, Streicher, Jenna, Stunnenberg, Henk, Tan, Kai, Taylor, Deanne, Thorogood, Adrian, Vallier, Ludovic, van Oudenaarden, Alexander, Watt, Fiona, Weicher, Wilko, Weissman, Jonathan, Wells, Andrew, Wold, Barbara, Xavier, Ramnik, Zhuang, Xiaowei, and Committee, Human Cell Atlas Organizing

Subjects
Quantitative Biology - Tissues and Organs
Abstract

The Human Cell Atlas (HCA) will be made up of comprehensive reference maps of all human cells - the fundamental units of life - as a basis for understanding fundamental human biological processes and diagnosing, monitoring, and treating disease. It will help scientists understand how genetic variants impact disease risk, define drug toxicities, discover better therapies, and advance regenerative medicine. A resource of such ambition and scale should be built in stages, increasing in size, breadth, and resolution as technologies develop and understanding deepens. We will therefore pursue Phase 1 as a suite of flagship projects in key tissues, systems, and organs. We will bring together experts in biology, medicine, genomics, technology development and computation (including data analysis, software engineering, and visualization). We will also need standardized experimental and computational methods that will allow us to compare diverse cell and tissue types - and samples across human communities - in consistent ways, ensuring that the resulting resource is truly global. This document, the first version of the HCA White Paper, was written by experts in the field with feedback and suggestions from the HCA community, gathered during recent international meetings. The White Paper, released at the close of this yearlong planning process, will be a living document that evolves as the HCA community provides additional feedback, as technological and computational advances are made, and as lessons are learned during the construction of the atlas.

Published
2018

17. Epiblast inducers capture mouse trophectoderm stem cells in vitro and pattern blastoids for implantation in utero

Author

Seong, Jinwoo, Frias-Aldeguer, Javier, Holzmann, Viktoria, Kagawa, Harunobu, Sestini, Giovanni, Heidari Khoei, Heidar, Scholte Op Reimer, Yvonne, Kip, Maarten, Pradhan, Saurabh J., Verwegen, Lucas, Vivié, Judith, Li, Linfeng, Alemany, Anna, Korving, Jeroen, Darmis, Frank, van Oudenaarden, Alexander, ten Berge, Derk, Geijsen, Niels, and Rivron, Nicolas C.

Published
2022
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22. Single-cell Ribo-seq reveals cell cycle-dependent translational pausing

Author

VanInsberghe, Michael, van den Berg, Jeroen, Andersson-Rolf, Amanda, Clevers, Hans, and van Oudenaarden, Alexander

Subjects
Physiological aspects, Genetic aspects, Research, Cell cycle -- Genetic aspects, Translation (Genetics) -- Research, Cytological research, Codons -- Physiological aspects, Genetic translation -- Research, Cell research, Codon -- Physiological aspects
Abstract

Author(s): Michael VanInsberghe [sup.1] , Jeroen van den Berg [sup.1] , Amanda Andersson-Rolf [sup.1] , Hans Clevers [sup.1] , Alexander van Oudenaarden [sup.1] Author Affiliations: (1) Oncode Institute, Hubrecht Institute-KNAW [...], Single-cell sequencing methods have enabled in-depth analysis of the diversity of cell types and cell states in a wide range of organisms. These tools focus predominantly on sequencing the genomes.sup.1, epigenomes.sup.2 and transcriptomes.sup.3 of single cells. However, despite recent progress in detecting proteins by mass spectrometry with single-cell resolution.sup.4, it remains a major challenge to measure translation in individual cells. Here, building on existing protocols.sup.5-7, we have substantially increased the sensitivity of these assays to enable ribosome profiling in single cells. Integrated with a machine learning approach, this technology achieves single-codon resolution. We validate this method by demonstrating that limitation for a particular amino acid causes ribosome pausing at a subset of the codons encoding the amino acid. Of note, this pausing is only observed in a sub-population of cells correlating to its cell cycle state. We further expand on this phenomenon in non-limiting conditions and detect pronounced GAA pausing during mitosis. Finally, we demonstrate the applicability of this technique to rare primary enteroendocrine cells. This technology provides a first step towards determining the contribution of the translational process to the remarkable diversity between seemingly identical cells. Highly sensitive ribosome profiling of single cells at single-codon resolution enables identification of distinct cell cycle-dependent translational dynamic states in individual cells.

Published
2021
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23. The Human Cell Atlas.

Author

Regev, Aviv, Teichmann, Sarah A, Lander, Eric S, Amit, Ido, Benoist, Christophe, Birney, Ewan, Bodenmiller, Bernd, Campbell, Peter, Carninci, Piero, Clatworthy, Menna, Clevers, Hans, Deplancke, Bart, Dunham, Ian, Eberwine, James, Eils, Roland, Enard, Wolfgang, Farmer, Andrew, Fugger, Lars, Göttgens, Berthold, Hacohen, Nir, Haniffa, Muzlifah, Hemberg, Martin, Kim, Seung, Klenerman, Paul, Kriegstein, Arnold, Lein, Ed, Linnarsson, Sten, Lundberg, Emma, Lundeberg, Joakim, Majumder, Partha, Marioni, John C, Merad, Miriam, Mhlanga, Musa, Nawijn, Martijn, Netea, Mihai, Nolan, Garry, Pe'er, Dana, Phillipakis, Anthony, Ponting, Chris P, Quake, Stephen, Reik, Wolf, Rozenblatt-Rosen, Orit, Sanes, Joshua, Satija, Rahul, Schumacher, Ton N, Shalek, Alex, Shapiro, Ehud, Sharma, Padmanee, Shin, Jay W, Stegle, Oliver, Stratton, Michael, Stubbington, Michael JT, Theis, Fabian J, Uhlen, Matthias, van Oudenaarden, Alexander, Wagner, Allon, Watt, Fiona, Weissman, Jonathan, Wold, Barbara, Xavier, Ramnik, Yosef, Nir, and Human Cell Atlas Meeting Participants

Subjects
Human Cell Atlas Meeting Participants, Eukaryotic Cells, Humans, Human Body, International Cooperation, Atlases as Topic, cell atlas, cell biology, computational biology, human, lineage, mouse, science forum, single-cell genomics, systems biology, Biochemistry and Cell Biology
Abstract

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

Published
2017

26. Acute multi-level response to defective de novo chromatin assembly in S-phase

Author

Dreyer, Jan, primary, Ricci, Giulia, additional, van den Berg, Jeroen, additional, Bhardwaj, Vivek, additional, Funk, Janina, additional, Armstrong, Claire, additional, van Batenburg, Vincent, additional, Sine, Chance, additional, Vaninsberghe, Michael A., additional, Marsman, Richard, additional, Mandemaker, Imke K., additional, di Sanzo, Simone, additional, Costantini, Juliette, additional, Manzo, Stefano, additional, Biran, Alva, additional, Burny, Claire, additional, Voelker-Albert, Moritz, additional, Groth, Anja, additional, Spencer, Sabrina L, additional, van Oudenaarden, Alexander, additional, and Mattiroli, Francesca, additional

Published
2024
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27. Differential stoichiometry among core ribosomal proteins

Author

Slavov, Nikolai, Semrau, Sefan, Airoldi, Edoardo, Budnik, Bogdan, and van Oudenaarden, Alexander

Subjects
Quantitative Biology - Genomics, Quantitative Biology - Biomolecules, Quantitative Biology - Molecular Networks, Quantitative Biology - Subcellular Processes
Abstract

Understanding the regulation and structure of ribosomes is essential to understanding protein synthesis and its deregulation in disease. While ribosomes are believed to have a fixed stoichiometry among their core ribosomal proteins (RPs), some experiments suggest a more variable composition. Testing such variability requires direct and precise quantification of RPs. We used mass-spectrometry to directly quantify RPs across monosomes and polysomes of mouse embryonic stem cells (ESC) and budding yeast. Our data show that the stoichiometry among core RPs in wild-type yeast cells and ESC depends both on the growth conditions and on the number of ribosomes bound per mRNA. Furthermore, we find that the fitness of cells with a deleted RP-gene is inversely proportional to the enrichment of the corresponding RP in polysomes. Together, our findings support the existence of ribosomes with distinct protein composition and physiological function., Comment: 31 pages, 8 figures

Published
2014
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29. Snake Venom Gland Organoids

Author

Post, Yorick, Puschhof, Jens, Beumer, Joep, Kerkkamp, Harald M., de Bakker, Merijn A.G., Slagboom, Julien, de Barbanson, Buys, Wevers, Nienke R., Spijkers, Xandor M., Olivier, Thomas, Kazandjian, Taline D., Ainsworth, Stuart, Iglesias, Carmen Lopez, van de Wetering, Willine J., Heinz, Maria C., van Ineveld, Ravian L., van Kleef, Regina G.D.M., Begthel, Harry, Korving, Jeroen, Bar-Ephraim, Yotam E., Getreuer, Walter, Rios, Anne C., Westerink, Remco H.S., Snippert, Hugo J.G., van Oudenaarden, Alexander, Peters, Peter J., Vonk, Freek J., Kool, Jeroen, Richardson, Michael K., Casewell, Nicholas R., and Clevers, Hans

Published
2020
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30. Quantifying DNA replication speeds in single cells by scEdU-seq

Author

CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, van den Berg, Jeroen, van Batenburg, Vincent, Geisenberger, Christoph, Tjeerdsma, Rinskje B., de Jaime-Soguero, Anchel, Acebrón, Sergio P., van Vugt, Marcel A.T.M., van Oudenaarden, Alexander, CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, van den Berg, Jeroen, van Batenburg, Vincent, Geisenberger, Christoph, Tjeerdsma, Rinskje B., de Jaime-Soguero, Anchel, Acebrón, Sergio P., van Vugt, Marcel A.T.M., and van Oudenaarden, Alexander

Published
2024

31. Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy

Author

CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Dias, Matheus Henrique, Friskes, Anoek, Wang, Siying, Fernandes Neto, Joao M., van Gemert, Frank, Mourragui, Soufiane, Papagianni, Chrysa, Kuiken, Hendrik J., Mainardi, Sara, Alvarez-Villanueva, Daniel, Lieftink, Cor, Morris, Ben, Dekker, Anna, van Dijk, Emma, Wilms, Lieke H.S., da Silva, Marcelo S., Jansen, Robin A., Mulero-Sánchez, Antonio, Malzer, Elke, Vidal, August, Santos, Cristina, Salazar, Ramón, Wailemann, Rosangela A.M., Torres, Thompson E.P., De Conti, Giulia, Raaijmakers, Jonne A., Snaebjornsson, Petur, Yuan, Shengxian, Qin, Wenxin, Kovach, John S., Armelin, Hugo A., Te Riele, Hein, van Oudenaarden, Alexander, Jin, Haojie, Beijersbergen, Roderick L., Villanueva, Alberto, Medema, Rene H., Bernards, Rene, CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Dias, Matheus Henrique, Friskes, Anoek, Wang, Siying, Fernandes Neto, Joao M., van Gemert, Frank, Mourragui, Soufiane, Papagianni, Chrysa, Kuiken, Hendrik J., Mainardi, Sara, Alvarez-Villanueva, Daniel, Lieftink, Cor, Morris, Ben, Dekker, Anna, van Dijk, Emma, Wilms, Lieke H.S., da Silva, Marcelo S., Jansen, Robin A., Mulero-Sánchez, Antonio, Malzer, Elke, Vidal, August, Santos, Cristina, Salazar, Ramón, Wailemann, Rosangela A.M., Torres, Thompson E.P., De Conti, Giulia, Raaijmakers, Jonne A., Snaebjornsson, Petur, Yuan, Shengxian, Qin, Wenxin, Kovach, John S., Armelin, Hugo A., Te Riele, Hein, van Oudenaarden, Alexander, Jin, Haojie, Beijersbergen, Roderick L., Villanueva, Alberto, Medema, Rene H., and Bernards, Rene

Published
2024

33. Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress

Author

CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, de Jaime-Soguero, Anchel, Hattemer, Janina, Bufe, Anja, Haas, Alexander, van den Berg, Jeroen, van Batenburg, Vincent, Das, Biswajit, di Marco, Barbara, Androulaki, Stefania, Böhly, Nicolas, Landry, Jonathan J.M., Schoell, Brigitte, Rosa, Viviane S., Villacorta, Laura, Baskan, Yagmur, Trapp, Marleen, Benes, Vladimir, Chabes, Andrei, Shahbazi, Marta, Jauch, Anna, Engel, Ulrike, Patrizi, Annarita, Sotillo, Rocio, van Oudenaarden, Alexander, Bageritz, Josephine, Alfonso, Julieta, Bastians, Holger, Acebrón, Sergio P., CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, de Jaime-Soguero, Anchel, Hattemer, Janina, Bufe, Anja, Haas, Alexander, van den Berg, Jeroen, van Batenburg, Vincent, Das, Biswajit, di Marco, Barbara, Androulaki, Stefania, Böhly, Nicolas, Landry, Jonathan J.M., Schoell, Brigitte, Rosa, Viviane S., Villacorta, Laura, Baskan, Yagmur, Trapp, Marleen, Benes, Vladimir, Chabes, Andrei, Shahbazi, Marta, Jauch, Anna, Engel, Ulrike, Patrizi, Annarita, Sotillo, Rocio, van Oudenaarden, Alexander, Bageritz, Josephine, Alfonso, Julieta, Bastians, Holger, and Acebrón, Sergio P.

Published
2024

34. Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis

Author

Hubrecht Institute with UMC, Gribaudo, Simona, Robert, Rémi, van Sambeek, Björn, Mirdass, Camil, Lyubimova, Anna, Bouhali, Kamal, Ferent, Julien, Morin, Xavier, van Oudenaarden, Alexander, Nedelec, Stéphane, Hubrecht Institute with UMC, Gribaudo, Simona, Robert, Rémi, van Sambeek, Björn, Mirdass, Camil, Lyubimova, Anna, Bouhali, Kamal, Ferent, Julien, Morin, Xavier, van Oudenaarden, Alexander, and Nedelec, Stéphane

Published
2024

35. LifeTime and improving European healthcare through cell-based interceptive medicine

Author

Rajewsky, Nikolaus, Almouzni, Geneviève, Gorski, Stanislaw A., Aerts, Stein, Amit, Ido, Bertero, Michela G., Bock, Christoph, Bredenoord, Annelien L., Cavalli, Giacomo, Chiocca, Susanna, Clevers, Hans, De Strooper, Bart, Eggert, Angelika, Ellenberg, Jan, Fernández, Xosé M., Figlerowicz, Marek, Gasser, Susan M., Hubner, Norbert, Kjems, Jørgen, Knoblich, Jürgen A., Krabbe, Grietje, Lichter, Peter, Linnarsson, Sten, Marine, Jean-Christophe, Marioni, John C., Marti-Renom, Marc A., Netea, Mihai G., Nickel, Dörthe, Nollmann, Marcelo, Novak, Halina R., Parkinson, Helen, Piccolo, Stefano, Pinheiro, Inês, Pombo, Ana, Popp, Christian, Reik, Wolf, Roman-Roman, Sergio, Rosenstiel, Philip, Schultze, Joachim L., Stegle, Oliver, Tanay, Amos, Testa, Giuseppe, Thanos, Dimitris, Theis, Fabian J., Torres-Padilla, Maria-Elena, Valencia, Alfonso, Vallot, Céline, van Oudenaarden, Alexander, Vidal, Marie, and Voet, Thierry

Published
2020
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45. Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

Author

Loomans, Cindy J.M., Williams Giuliani, Nerys, Balak, Jeetindra, Ringnalda, Femke, van Gurp, Léon, Huch, Meritxell, Boj, Sylvia F., Sato, Toshiro, Kester, Lennart, de Sousa Lopes, Susana M. Chuva, Roost, Matthias S., Bonner-Weir, Susan, Engelse, Marten A., Rabelink, Ton J., Heimberg, Harry, Vries, Robert G.J., van Oudenaarden, Alexander, Carlotti, Françoise, Clevers, Hans, and de Koning, Eelco J.P.

Published
2018
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46. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity

Author

Kopper, Oded, de Witte, Chris J., Lõhmussaar, Kadi, Valle-Inclan, Jose Espejo, Hami, Nizar, Kester, Lennart, Balgobind, Anjali Vanita, Korving, Jeroen, Proost, Natalie, Begthel, Harry, van Wijk, Lise M., Revilla, Sonia Aristín, Theeuwsen, Rebecca, van de Ven, Marieke, van Roosmalen, Markus J., Ponsioen, Bas, Ho, Victor W. H., Neel, Benjamin G., Bosse, Tjalling, Gaarenstroom, Katja N., Vrieling, Harry, Vreeswijk, Maaike P. G., van Diest, Paul J., Witteveen, Petronella O., Jonges, Trudy, Bos, Johannes L., van Oudenaarden, Alexander, Zweemer, Ronald P., Snippert, Hugo J. G., Kloosterman, Wigard P., and Clevers, Hans

Published
2019
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47. Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids

Author

Bolhaqueiro, Ana C. F., Ponsioen, Bas, Bakker, Bjorn, Klaasen, Sjoerd J., Kucukkose, Emre, van Jaarsveld, Richard H., Vivié, Judith, Verlaan-Klink, Ingrid, Hami, Nizar, Spierings, Diana C. J., Sasaki, Nobuo, Dutta, Devanjali, Boj, Sylvia F., Vries, Robert G. J., Lansdorp, Peter M., van de Wetering, Marc, van Oudenaarden, Alexander, Clevers, Hans, Kranenburg, Onno, Foijer, Floris, Snippert, Hugo J. G., and Kops, Geert J. P. L.

Published
2019
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48. A physical sciences network characterization of non-tumorigenic and metastatic cells

Author

Agus, David B, Alexander, Jenolyn F, Arap, Wadih, Ashili, Shashanka, Aslan, Joseph E, Austin, Robert H, Backman, Vadim, Bethel, Kelly J, Bonneau, Richard, Chen, Wei-Chiang, Chen-Tanyolac, Chira, Choi, Nathan C, Curley, Steven A, Dallas, Matthew, Damania, Dhwanil, Davies, Paul CW, Decuzzi, Paolo, Dickinson, Laura, Estevez-Salmeron, Luis, Estrella, Veronica, Ferrari, Mauro, Fischbach, Claudia, Foo, Jasmine, Fraley, Stephanie I, Frantz, Christian, Fuhrmann, Alexander, Gascard, Philippe, Gatenby, Robert A, Geng, Yue, Gerecht, Sharon, Gillies, Robert J, Godin, Biana, Grady, William M, Greenfield, Alex, Hemphill, Courtney, Hempstead, Barbara L, Hielscher, Abigail, Hillis, W Daniel, Holland, Eric C, Ibrahim-Hashim, Arig, Jacks, Tyler, Johnson, Roger H, Joo, Ahyoung, Katz, Jonathan E, Kelbauskas, Laimonas, Kesselman, Carl, King, Michael R, Konstantopoulos, Konstantinos, Kraning-Rush, Casey M, Kuhn, Peter, Kung, Kevin, Kwee, Brian, Lakins, Johnathon N, Lambert, Guillaume, Liao, David, Licht, Jonathan D, Liphardt, Jan T, Liu, Liyu, Lloyd, Mark C, Lyubimova, Anna, Mallick, Parag, Marko, John, McCarty, Owen JT, Meldrum, Deirdre R, Michor, Franziska, Mumenthaler, Shannon M, Nandakumar, Vivek, O’Halloran, Thomas V, Oh, Steve, Pasqualini, Renata, Paszek, Matthew J, Philips, Kevin G, Poultney, Christopher S, Rana, Kuldeepsinh, Reinhart-King, Cynthia A, Ros, Robert, Semenza, Gregg L, Senechal, Patti, Shuler, Michael L, Srinivasan, Srimeenakshi, Staunton, Jack R, Stypula, Yolanda, Subramanian, Hariharan, Tlsty, Thea D, Tormoen, Garth W, Tseng, Yiider, van Oudenaarden, Alexander, Verbridge, Scott S, Wan, Jenny C, Weaver, Valerie M, Widom, Jonathan, Will, Christine, Wirtz, Denis, Wojtkowiak, Jonathan, and Wu, Pei-Hsun

Subjects
Biochemistry and Cell Biology, Biological Sciences, Cancer, Breast Cancer, Women's Health, 2.1 Biological and endogenous factors, Biomarkers, Tumor, Cell Line, Tumor, Cell Movement, Cell Size, Cell Survival, Computer Simulation, Gene Expression Regulation, Neoplastic, Humans, Models, Biological, Neoplasm Metastasis, Neoplasm Proteins, Physical Sciences - Oncology Centers Network
Abstract

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

Published
2013

49. A physical sciences network characterization of non-tumorigenic and metastatic cells.

Author

Physical Sciences - Oncology Centers Network, Agus, David B, Alexander, Jenolyn F, Arap, Wadih, Ashili, Shashanka, Aslan, Joseph E, Austin, Robert H, Backman, Vadim, Bethel, Kelly J, Bonneau, Richard, Chen, Wei-Chiang, Chen-Tanyolac, Chira, Choi, Nathan C, Curley, Steven A, Dallas, Matthew, Damania, Dhwanil, Davies, Paul CW, Decuzzi, Paolo, Dickinson, Laura, Estevez-Salmeron, Luis, Estrella, Veronica, Ferrari, Mauro, Fischbach, Claudia, Foo, Jasmine, Fraley, Stephanie I, Frantz, Christian, Fuhrmann, Alexander, Gascard, Philippe, Gatenby, Robert A, Geng, Yue, Gerecht, Sharon, Gillies, Robert J, Godin, Biana, Grady, William M, Greenfield, Alex, Hemphill, Courtney, Hempstead, Barbara L, Hielscher, Abigail, Hillis, W Daniel, Holland, Eric C, Ibrahim-Hashim, Arig, Jacks, Tyler, Johnson, Roger H, Joo, Ahyoung, Katz, Jonathan E, Kelbauskas, Laimonas, Kesselman, Carl, King, Michael R, Konstantopoulos, Konstantinos, Kraning-Rush, Casey M, Kuhn, Peter, Kung, Kevin, Kwee, Brian, Lakins, Johnathon N, Lambert, Guillaume, Liao, David, Licht, Jonathan D, Liphardt, Jan T, Liu, Liyu, Lloyd, Mark C, Lyubimova, Anna, Mallick, Parag, Marko, John, McCarty, Owen JT, Meldrum, Deirdre R, Michor, Franziska, Mumenthaler, Shannon M, Nandakumar, Vivek, O'Halloran, Thomas V, Oh, Steve, Pasqualini, Renata, Paszek, Matthew J, Philips, Kevin G, Poultney, Christopher S, Rana, Kuldeepsinh, Reinhart-King, Cynthia A, Ros, Robert, Semenza, Gregg L, Senechal, Patti, Shuler, Michael L, Srinivasan, Srimeenakshi, Staunton, Jack R, Stypula, Yolanda, Subramanian, Hariharan, Tlsty, Thea D, Tormoen, Garth W, Tseng, Yiider, van Oudenaarden, Alexander, Verbridge, Scott S, Wan, Jenny C, Weaver, Valerie M, Widom, Jonathan, Will, Christine, Wirtz, Denis, Wojtkowiak, Jonathan, and Wu, Pei-Hsun

Subjects
Physical Sciences - Oncology Centers Network, Cell Line, Tumor, Humans, Neoplasm Metastasis, Neoplasm Proteins, Cell Movement, Cell Size, Cell Survival, Gene Expression Regulation, Neoplastic, Models, Biological, Computer Simulation, Biomarkers, Tumor, Cancer, Breast Cancer, Biotechnology, 2.1 Biological and endogenous factors
Abstract

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

Published
2013

50. A novel sperm-delivered toxin causes late-stage embryo lethality and transmission ratio distortion in C. elegans.

Author

Seidel, Hannah S, Ailion, Michael, Li, Jialing, van Oudenaarden, Alexander, Rockman, Matthew V, and Kruglyak, Leonid

Subjects
Muscles, Spermatozoa, Epidermis, Organelles, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Membrane Proteins, Phylogeny, Heredity, Amino Acid Sequence, Protein Structure, Tertiary, Embryonic Development, Gene Dosage, Phenotype, Genes, Lethal, Molecular Sequence Data, Female, Male, Toxins, Biological, Genetic Linkage, Genes, Lethal, Protein Structure, Tertiary, Toxins, Biological, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Developmental Biology
Abstract

The evolutionary fate of an allele ordinarily depends on its contribution to host fitness. Occasionally, however, genetic elements arise that are able to gain a transmission advantage while simultaneously imposing a fitness cost on their hosts. We previously discovered one such element in C. elegans that gains a transmission advantage through a combination of paternal-effect killing and zygotic self-rescue. Here we demonstrate that this element is composed of a sperm-delivered toxin, peel-1, and an embryo-expressed antidote, zeel-1. peel-1 and zeel-1 are located adjacent to one another in the genome and co-occur in an insertion/deletion polymorphism. peel-1 encodes a novel four-pass transmembrane protein that is expressed in sperm and delivered to the embryo via specialized, sperm-specific vesicles. In the absence of zeel-1, sperm-delivered PEEL-1 causes lethal defects in muscle and epidermal tissue at the 2-fold stage of embryogenesis. zeel-1 is expressed transiently in the embryo and encodes a novel six-pass transmembrane domain fused to a domain with sequence similarity to zyg-11, a substrate-recognition subunit of an E3 ubiquitin ligase. zeel-1 appears to have arisen recently, during an expansion of the zyg-11 family, and the transmembrane domain of zeel-1 is required and partially sufficient for antidote activity. Although PEEL-1 and ZEEL-1 normally function in embryos, these proteins can act at other stages as well. When expressed ectopically in adults, PEEL-1 kills a variety of cell types, and ectopic expression of ZEEL-1 rescues these effects. Our results demonstrate that the tight physical linkage between two novel transmembrane proteins has facilitated their co-evolution into an element capable of promoting its own transmission to the detriment of organisms carrying it.

Published
2011

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