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2. Structure, interaction and nervous connectivity of beta cell primary cilia

Author

Müller, Andreas, Klena, Nikolai, Pang, Song, Garcia, Leticia Elizabeth Galicia, Topcheva, Oleksandra, Aurrecoechea Duran, Solange, Sulaymankhil, Davud, Seliskar, Monika, Mziaut, Hassan, Schöniger, Eyke, Friedland, Daniela, Kipke, Nicole, Kretschmar, Susanne, Münster, Carla, Weitz, Jürgen, Distler, Marius, Kurth, Thomas, Schmidt, Deborah, Hess, Harald F., Xu, C. Shan, Pigino, Gaia, and Solimena, Michele

Published
2024
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3. Organelle-specific segmentation, spatial analysis, and visualization of volume electron microscopy datasets

Author

Müller, Andreas, Schmidt, Deborah, Rieckert, Lucas, Solimena, Michele, and Weigert, Martin

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning, Quantitative Biology - Quantitative Methods
Abstract

Volume electron microscopy is the method of choice for the in-situ interrogation of cellular ultrastructure at the nanometer scale. Recent technical advances have led to a rapid increase in large raw image datasets that require computational strategies for segmentation and spatial analysis. In this protocol, we describe a practical and annotation-efficient pipeline for organelle-specific segmentation, spatial analysis, and visualization of large volume electron microscopy datasets using freely available, user-friendly software tools that can be run on a single standard workstation. We specifically target researchers in the life sciences with limited computational expertise, who face the following tasks within their volume electron microscopy projects: i) How to generate 3D segmentation labels for different types of cell organelles while minimizing manual annotation efforts, ii) how to analyze the spatial interactions between organelle instances, and iii) how to best visualize the 3D segmentation results. To meet these demands we give detailed guidelines for choosing the most efficient segmentation tools for the specific cell organelle. We furthermore provide easily executable components for spatial analysis and 3D rendering and bridge compatibility issues between freely available open-source tools, such that others can replicate our full pipeline starting from a raw dataset up to the final plots and rendered images. We believe that our detailed description can serve as a valuable reference for similar projects requiring special strategies for single- or multiple organelle analysis which can be achieved with computational resources commonly available to single-user setups.

Published
2023

5. Every islet matters: improving the impact of human islet research.

Author

Gloyn, Anna, Ibberson, Mark, Marchetti, Piero, Powers, Alvin, Rorsman, Patrik, Sander, Maike, and Solimena, Michele

Subjects
Diabetes Mellitus, Type 2, Humans, Islets of Langerhans, Islets of Langerhans Transplantation, Living Donors, Pancreas
Abstract

Detailed characterization of human pancreatic islets is key to elucidating the pathophysiology of all forms of diabetes, especially type 2 diabetes. However, access to human pancreatic islets is limited. Pancreatic tissue for islet retrieval can be obtained from brain-dead organ donors or from individuals undergoing pancreatectomy, often referred to as living donors. Different protocols for human islet procurement can substantially impact islet function. This variability, coupled with heterogeneity between individuals and islets, results in analytical challenges to separate genuine disease pathology or differences between human donors from experimental noise. There are currently no international guidelines for human donor phenotyping, islet procurement and functional characterization. This lack of standardization means that substantial investments from multiple international efforts towards improved understanding of diabetes pathology cannot be fully leveraged. In this Perspective, we overview the status of the field of human islet research, highlight the challenges and propose actions that could accelerate research progress and increase understanding of type 2 diabetes to slow its pandemic spreading.

Published
2022

9. Identification of biomarkers for glycaemic deterioration in type 2 diabetes

Author

Slieker, Roderick C., Donnelly, Louise A., Akalestou, Elina, Lopez-Noriega, Livia, Melhem, Rana, Güneş, Ayşim, Abou Azar, Frederic, Efanov, Alexander, Georgiadou, Eleni, Muniangi-Muhitu, Hermine, Sheikh, Mahsa, Giordano, Giuseppe N., Åkerlund, Mikael, Ahlqvist, Emma, Ali, Ashfaq, Banasik, Karina, Brunak, Søren, Barovic, Marko, Bouland, Gerard A., Burdet, Frédéric, Canouil, Mickaël, Dragan, Iulian, Elders, Petra J. M., Fernandez, Celine, Festa, Andreas, Fitipaldi, Hugo, Froguel, Phillippe, Gudmundsdottir, Valborg, Gudnason, Vilmundur, Gerl, Mathias J., van der Heijden, Amber A., Jennings, Lori L., Hansen, Michael K., Kim, Min, Leclerc, Isabelle, Klose, Christian, Kuznetsov, Dmitry, Mansour Aly, Dina, Mehl, Florence, Marek, Diana, Melander, Olle, Niknejad, Anne, Ottosson, Filip, Pavo, Imre, Duffin, Kevin, Syed, Samreen K., Shaw, Janice L., Cabrera, Over, Pullen, Timothy J., Simons, Kai, Solimena, Michele, Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Lim, Gareth E., Estall, Jennifer, Ibberson, Mark, Beulens, Joline W. J., ’t Hart, Leen M, Pearson, Ewan R., and Rutter, Guy A.

Published
2023
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10. Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS)

Author

Sandforth, Arvid, von Schwartzenberg, Reiner Jumpertz, Arreola, Elsa Vazquez, Hanson, Robert L, Sancar, Gencer, Katzenstein, Sarah, Lange, Karl, Preißl, Hubert, Dreher, Simon I, Weigert, Cora, Wagner, Robert, Kantartzis, Kostantinos, Machann, Jürgen, Schick, Fritz, Lehmann, Rainer, Peter, Andreas, Katsouli, Nikoletta, Ntziachristos, Vasilis, Dannecker, Corinna, Fritsche, Louise, Perakakis, Nikolaos, Heni, Martin, Nawroth, Peter Paul, Kopf, Stefan, Pfeiffer, Andreas F H, Kabisch, Stefan, Stumvoll, Michael, Schwarz, Peter E H, Hauner, Hans, Lechner, Andreas, Seissler, Jochen, Yurchenko, Iryna, Icks, Andrea, Solimena, Michele, Häring, Hans-Ulrich, Szendroedi, Julia, Schürmann, Annette, de Angelis, Martin Hrabé, Blüher, Matthias, Roden, Michael, Bornstein, Stefan R, Stefan, Norbert, Fritsche, Andreas, and Birkenfeld, Andreas L

Published
2023
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11. Mechanisms and clinical relevance of the bidirectional relationship of viral infections with metabolic diseases

Author

Perakakis, Nikolaos, Harb, Hani, Hale, Benjamin G, Varga, Zsuzsanna, Steenblock, Charlotte, Kanczkowski, Waldemar, Alexaki, Vasileia Ismini, Ludwig, Barbara, Mirtschink, Peter, Solimena, Michele, Toepfner, Nicole, Zeissig, Sebastian, Gado, Manuel, Abela, Irene Alma, Beuschlein, Felix, Spinas, Giatgen A, Cavelti-Weder, Claudia, Gerber, Philipp A, Huber, Michael, Trkola, Alexandra, Puhan, Milo A, Wong, Wendy Wei-Lynn, Linkermann, Andreas, Mohan, Viswanathan, Lehnert, Hendrik, Nawroth, Peter, Chavakis, Triantafyllos, Mingrone, Geltrude, Wolfrum, Christian, Zinkernagel, Annelies S, and Bornstein, Stefan R

Published
2023
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12. Gene expression signature predicts rate of type 1 diabetes progression

Author

Mathieu, Chantal, Gillard, Pieter, Casteels, Kristina, Overbergh, Lutgart, Dunger, David, Wallace, Chris, Evans, Mark, Thankamony, Ajay, Hendriks, Emile, Bruggraber, Sylvaine, Marcoveccchio, Loredana, Peakman, Mark, Tree, Timothy, Morgan, Noel G., Richardson, Sarah, Todd, John A., Wicker, Linda, Mander, Adrian, Dayan, Colin, Alhadj Ali, Mohammad, Pieber, Thomas, Eizirik, Decio L., Cnop, Myriam, Brunak, Søren, Pociot, Flemming, Johannesen, Jesper, Rossing, Peter, Quigley, Cristina Legido, Mallone, Roberto, Scharfmann, Raphael, Boitard, Christian, Knip, Mikael, Otonkoski, Timo, Veijola, Riitta, Lahesmaa, Riitta, Oresic, Matej, Toppari, Jorma, Danne, Thomas, Ziegler, Anette G., Achenbach, Peter, Rodriguez-Calvo, Teresa, Solimena, Michele, Bonifacio, Ezio E., Speier, Stephan, Holl, Reinhard, Dotta, Francesco, Chiarelli, Francesco, Marchetti, Piero, Bosi, Emanuele, Cianfarani, Stefano, Ciampalini, Paolo, De Beaufort, Carine, Dahl-Jørgensen, Knut, Skrivarhaug, Torild, Joner, Geir, Krogvold, Lars, Jarosz-Chobot, Przemka, Battelino, Tadej, Thorens, Bernard, Gotthardt, Martin, Roep, Bart O., Nikolic, Tanja, Zaldumbide, Arnaud, Lernmark, Ake, Lundgren, Marcus, Costacalde, Guillaume, Strube, Thorsten, Schulte, Anke M., Nitsche, Almut, Vela, Jose, Von Herrath, Matthias, Wesley, Johnna, Napolitano-Rosen, Antonella, Thomas, Melissa, Schloot, Nanette, Goldfine, Allison, Waldron-Lynch, Frank, Kompa, Jill, Vedala, Aruna, Hartmann, Nicole, Nicolas, Gwenaelle, van Rampelbergh, Jean, Bovy, Nicolas, Dutta, Sanjoy, Soderberg, Jeannette, Ahmed, Simi, Martin, Frank, Latres, Esther, Agiostratidou, Gina, Koralova, Anne, Willemsen, Ruben, Smith, Anne, Anand, Binu, Datta, Vipan, Puthi, Vijith, Zac-Varghese, Sagen, Dias, Renuka, Sundaram, Premkumar, Vaidya, Bijay, Patterson, Catherine, Owen, Katharine, Piel, Barbara, Heller, Simon, Randell, Tabitha, Gazis, Tasso, Reismen, Elise Bismuth, Carel, Jean-Claude, Riveline, Jean-Pierre, Gautier, Jean-Francoise, Andreelli, Fabrizion, Travert, Florence, Cosson, Emmanuel, Penfornis, Alfred, Petit, Catherine, Feve, Bruno, Lucidarme, Nadine, Beressi, Jean-Paul, Ajzenman, Catherina, Radu, Alina, Greteau-Hamoumou, Stephanie, Bibal, Cecile, Meissner, Thomas, Heidtmann, Bettina, Toni, Sonia, Rami-Merhar, Birgit, Eeckhout, Bart, Peene, Bernard, Vantongerloo, N., Maes, Toon, Gommers, Leen, Suomi, Tomi, Starskaia, Inna, Kalim, Ubaid Ullah, Rasool, Omid, Jaakkola, Maria K., Grönroos, Toni, Välikangas, Tommi, Brorsson, Caroline, Mazzoni, Gianluca, Overbergh, Lut, Chmura, Piotr, and Elo, Laura L.

Published
2023
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15. PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents

Author

Rehn, Matilda, Wenzel, Anne, Frank, Anne-Katrine, Schuster, Mikkel Bruhn, Pundhir, Sachin, Jørgensen, Nanna, Vitting-Seerup, Kristoffer, Ge, Ying, Jendholm, Johan, Michaut, Magali, Schoof, Erwin M., Jensen, Tanja Lyholm, Rapin, Nicolas, Sapio, Russell T., Andersen, Kasper Langebjerg, Lund, Anders H., Solimena, Michele, Holzenberger, Martin, Pestov, Dimitri G., and Porse, Bo Torben

Published
2022
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17. Metabolic implications of pancreatic fat accumulation

Author

Wagner, Robert, Eckstein, Sabine S., Yamazaki, Hajime, Gerst, Felicia, Machann, Jürgen, Jaghutriz, Benjamin Assad, Schürmann, Annette, Solimena, Michele, Singer, Stephan, Königsrainer, Alfred, Birkenfeld, Andreas L., Häring, Hans-Ulrich, Fritsche, Andreas, Ullrich, Susanne, and Heni, Martin

Published
2022
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19. An open-access volume electron microscopy atlas of whole cells and tissues

Author

Xu, C. Shan, Pang, Song, Shtengel, Gleb, Müller, Andreas, Ritter, Alex T., Hoffman, Huxley K., Takemura, Shin-ya, Lu, Zhiyuan, Pasolli, H. Amalia, Iyer, Nirmala, Chung, Jeeyun, Bennett, Davis, Weigel, Aubrey V., Freeman, Melanie, van Engelenburg, Schuyler B., Walther, Tobias C., Farese, Jr., Robert V., Lippincott-Schwartz, Jennifer, Mellman, Ira, Solimena, Michele, and Hess, Harald F.

Published
2021
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22. Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes

Author

Wigger, Leonore, Barovic, Marko, Brunner, Andreas-David, Marzetta, Flavia, Schöniger, Eyke, Mehl, Florence, Kipke, Nicole, Friedland, Daniela, Burdet, Frederic, Kessler, Camille, Lesche, Mathias, Thorens, Bernard, Bonifacio, Ezio, Legido-Quigley, Cristina, Barbier Saint Hilaire, Pierre, Delerive, Philippe, Dahl, Andreas, Klose, Christian, Gerl, Mathias J., Simons, Kai, Aust, Daniela, Weitz, Jürgen, Distler, Marius, Schulte, Anke M., Mann, Matthias, Ibberson, Mark, and Solimena, Michele

Published
2021
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23. Persistent or Transient Human β Cell Dysfunction Induced by Metabolic Stress: Specific Signatures and Shared Gene Expression with Type 2 Diabetes

Author

Marselli, Lorella, Piron, Anthony, Suleiman, Mara, Colli, Maikel L., Yi, Xiaoyan, Khamis, Amna, Carrat, Gaelle R., Rutter, Guy A., Bugliani, Marco, Giusti, Laura, Ronci, Maurizio, Ibberson, Mark, Turatsinze, Jean-Valery, Boggi, Ugo, De Simone, Paolo, De Tata, Vincenzo, Lopes, Miguel, Nasteska, Daniela, De Luca, Carmela, Tesi, Marta, Bosi, Emanuele, Singh, Pratibha, Campani, Daniela, Schulte, Anke M., Solimena, Michele, Hecht, Peter, Rady, Brian, Bakaj, Ivona, Pocai, Alessandro, Norquay, Lisa, Thorens, Bernard, Canouil, Mickaël, Froguel, Philippe, Eizirik, Decio L., Cnop, Miriam, and Marchetti, Piero

Published
2020
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24. The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis

Author

Carrat, Gaelle R., Haythorne, Elizabeth, Tomas, Alejandra, Haataja, Leena, Müller, Andreas, Arvan, Peter, Piunti, Alexandra, Cheng, Kaiying, Huang, Mutian, Pullen, Timothy J., Georgiadou, Eleni, Stylianides, Theodoros, Amirruddin, Nur Shabrina, Salem, Victoria, Distaso, Walter, Cakebread, Andrew, Heesom, Kate J., Lewis, Philip A., Hodson, David J., Briant, Linford J., Fung, Annie C.H., Sessions, Richard B., Alpy, Fabien, Kong, Alice P.S., Benke, Peter I., Torta, Federico, Teo, Adrian Kee Keong, Leclerc, Isabelle, Solimena, Michele, Wigley, Dale B., and Rutter, Guy A.

Published
2020
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25. Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice

Author

Carrat, Gaelle R, Hu, Ming, Nguyen-Tu, Marie-Sophie, Chabosseau, Pauline, Gaulton, Kyle J, van de Bunt, Martijn, Siddiq, Afshan, Falchi, Mario, Thurner, Matthias, Canouil, Mickaël, Pattou, Francois, Leclerc, Isabelle, Pullen, Timothy J, Cane, Matthew C, Prabhala, Priyanka, Greenwald, William, Schulte, Anke, Marchetti, Piero, Ibberson, Mark, MacDonald, Patrick E, Fox, Jocelyn E Manning, Gloyn, Anna L, Froguel, Philippe, Solimena, Michele, McCarthy, Mark I, and Rutter, Guy A

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Genetics, Biological Sciences, Human Genome, Diabetes, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adaptor Proteins, Signal Transducing, Alleles, Animals, Carrier Proteins, Cloning, Molecular, Diabetes Mellitus, Type 2, GTPase-Activating Proteins, Gene Expression Regulation, Genetic Variation, Homeostasis, Humans, Insulin, Insulin Secretion, Insulin-Secreting Cells, Liver, Mice, Phosphoproteins, Proinsulin, Quantitative Trait Loci, Transcriptome, ARAP1, GWAS, STARD10, diabetes, genetics, insulin, islet, mouse, secretion, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk. The risk alleles impair glucose-induced insulin secretion and, paradoxically but characteristically, are associated with decreased proinsulin:insulin ratios, indicating improved proinsulin conversion. Neither the identity of the causal variants nor the gene(s) through which risk is conferred have been firmly established. Whereas ARAP1 encodes a GTPase activating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer protein family. By integrating genetic fine-mapping and epigenomic annotation data and performing promoter-reporter and chromatin conformational capture (3C) studies in β cell lines, we localize the causal variant(s) at this locus to a 5 kb region that overlaps a stretch-enhancer active in islets. This region contains several highly correlated T2D-risk variants, including the rs140130268 indel. Expression QTL analysis of islet transcriptomes from three independent subject groups demonstrated that T2D-risk allele carriers displayed reduced levels of STARD10 mRNA, with no concomitant change in ARAP1 mRNA levels. Correspondingly, β-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion and recapitulated the pattern of improved proinsulin processing observed at the human GWAS signal. Conversely, overexpression of StarD10 in the adult β cell improved glucose tolerance in high fat-fed animals. In contrast, manipulation of Arap1 in β cells had no impact on insulin secretion or proinsulin conversion in mice. This convergence of human and murine data provides compelling evidence that the T2D risk associated with variation at this locus is mediated through reduction in STARD10 expression in the β cell.

Published
2017

26. Post-transcriptional regulation of insulin mRNA storage by G3BP1/2+ condensates in beta cells

Author

Quezada, Esteban, primary, Vasiljević, Jovana, additional, Pal, Akshaye, additional, Münster, Carla, additional, Friedland, Daniela, additional, Schöniger, Eyke, additional, Sönmez, Anke, additional, Seiler, Annika, additional, Roch, Pascal, additional, Wegbrod, Carolin, additional, Ganß, Katharina, additional, Knoch, Klaus-Peter, additional, Kipke, Nicole, additional, Alberti, Simon, additional, Nano, Rita, additional, Piemonti, Lorenzo, additional, Aust, Daniela, additional, Weitz, Jürgen, additional, Distler, Marius, additional, and Solimena, Michele, additional

Published
2024
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29. Post-transcriptional regulation of insulin mRNA mediated by G3BP1/2 condensates in beta cell biology

Author

Solimena, Michele, Alberti, Simon, Technische Universität Dresden, Quezada Dulcic, Esteban, Solimena, Michele, Alberti, Simon, Technische Universität Dresden, and Quezada Dulcic, Esteban

Abstract

Type 2 diabetes (T2D) is a prevalent metabolic disorder affecting approximately 529 million people globally, with an estimated increase to 1.27 billion by 2050. This condition is characterized by chronic, uncontrolled hyperglycemia, resulting from insufficient insulin secretion by pancreatic beta cells in relationship to metabolic needs due to elevated insulin resistance. Accordingly, a reduction of the functional beta cell mass is a key aspect of T2D pathogenesis. Recently, our transcriptomic analyses of laser-captured micro-dissected pancreatic islets from human living donors, identified G3BP1, which codes for a RNA-binding protein, to be among the most significantly downregulated genes in donors with T2D compared to normoglycemic individuals. This finding prompted us to investigate the role of G3BP1 in pancreatic beta cell function. Beta cells are specialized in maintaining glucose homeostasis, secreting insulin into the bloodstream in response to elevated blood glucose levels. These cells synthesize insulin at an impressive rate, exceeding 3,000 molecules per minute per cell. Given that insulin transcription is not immediate post-glucose stimulation, the regulation of insulin mRNA translation relies predominantly on post-transcriptional mechanisms. Several RNA-binding proteins (RBPs) have been identified to regulate insulin mRNA translation, notably PTBP1, which binds to the 3’ and 5’ UTRs, enhancing translation and stabilizing the transcript. Building on this, our research focused on evaluating the potential function of the RBP G3BP1 in beta cell function. G3BP1 is prominently known for its role in the formation of stress granules, membraneless phase-separated bodies comprising various mRNAs, small ribosomal subunits (40S), and RBPs. Their primary function is to halt translation, conserving energy during stress. However, our previous findings indicated the presence of G3BP1+ condensates under resting glucose concentrations, suggesting a non-stress induced respo, Typ-2-Diabetes (T2D) ist eine weit verbreitete Stoffwechselerkrankung, von der weltweit etwa 529 Millionen Menschen betroffen sind, mit einer geschätzten Zunahme auf 1,27 Milliarden bis 2050. Diese Erkrankung ist gekennzeichnet durch chronische, unkontrollierte Hyperglykämie, die auf unzureichende Insulinsekretion durch pankreatische Betazellen im Verhältnis zu den metabolischen Bedürfnissen des Organismus aufgrund erhöhter Insulinresistenz peripheren Gewebes zurückzuführen ist. Entsprechend ist eine Reduktion der funktionellen Betazellmasse ein Schlüsselaspekt der T2D-Pathogenese. Kürzlich identifizierten unsere transkriptomischen Analysen aus Laser mikrodissezierten Pankreasinseln von lebenden menschlichen Spendern G3BP1, eine Gensequenz welche ein RNA-bindendes Protein kodiert, als eines der am stärksten herunterregulierten Gene bei Spendern mit T2D im Vergleich zu normoglykämischen Individuen. Dieser Befund veranlasste uns, die Rolle von G3BP1 in der Funktion von Betazellen zu untersuchen. Betazellen sind darauf spezialisiert, die Glukosehomöostase aufrechtzuerhalten, indem sie Insulin in den Blutkreislauf abgeben, wenn der Blutzuckerspiegel erhöht ist. Diese Zellen synthetisieren Insulin mit einer beeindruckenden Rate, die mehr als 3.000 Moleküle pro Minute pro Zelle übersteigt. Da die Insulintranskription nach Glukosestimulation nicht sofort eintritt, beruht die Regulation der Insulin-mRNA-Übersetzung hauptsächlich auf posttranskriptionellen Mechanismen. Mehrere RNA-bindende Proteine (RBPs) wurden identifiziert, welche die Insulin-mRNA-Übersetzung regulieren. Unteranderem PTBP1, das an die 3’- und 5’-UTRs bindet, und so die Translation verstärkt und das Transkript stabilisiert. Aufbauend darauf konzentrierte sich unsere Forschung auf die Bewertung der potenziellen Funktion des RBP G3BP1 in Betazellen. G3BP1 ist vor allem für seine Rolle bei der Bildung von Stressgranula bekannt. Diese sind membranlose, phasenseparierte Kondensate, die aus verschiedenen mRNAs

Published
2024

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Author

Vecchio, Federica, Carré, Alexia, Korenkov, Daniil, Zhou, Zhicheng, Apaolaza, Paola, Tuomela, Soile, Burgos-Morales, Orlando, Snowhite, Isaac, Perez-Hernandez, Javier, Brandao, Barbara, Afonso, Georgia, Halliez, Clémentine, Kaddis, John, Kent, Sally C., Nakayama, Maki, Richardson, Sarah J., Vinh, Joelle, Verdier, Yann, Laiho, Jutta, Scharfmann, Raphael, Solimena, Michele, Marinicova, Zuzana, Bismuth, Elise, Lucidarme, Nadine, Sanchez, Janine, Bustamante, Carmen, Gomez, Patricia, Buus, Soren, You, Sylvaine, Pugliese, Alberto, Hyoty, Heikki, Rodriguez-Calvo, Teresa, Flodstrom-Tullberg, Malin, Mallone, Roberto, Vecchio, Federica, Carré, Alexia, Korenkov, Daniil, Zhou, Zhicheng, Apaolaza, Paola, Tuomela, Soile, Burgos-Morales, Orlando, Snowhite, Isaac, Perez-Hernandez, Javier, Brandao, Barbara, Afonso, Georgia, Halliez, Clémentine, Kaddis, John, Kent, Sally C., Nakayama, Maki, Richardson, Sarah J., Vinh, Joelle, Verdier, Yann, Laiho, Jutta, Scharfmann, Raphael, Solimena, Michele, Marinicova, Zuzana, Bismuth, Elise, Lucidarme, Nadine, Sanchez, Janine, Bustamante, Carmen, Gomez, Patricia, Buus, Soren, You, Sylvaine, Pugliese, Alberto, Hyoty, Heikki, Rodriguez-Calvo, Teresa, Flodstrom-Tullberg, Malin, and Mallone, Roberto

Published
2024

31. Modular segmentation, spatial analysis and visualization of volume electron microscopy datasets

Author

Mueller, Andreas, Schmidt, Deborah, Albrecht, Jan Philipp, Rieckert, Lucas, Otto, Maximilian, Galicia Garcia, Leticia Elizabeth, Fabig, Gunar, Solimena, Michele, Weigert, Martin, Mueller, Andreas, Schmidt, Deborah, Albrecht, Jan Philipp, Rieckert, Lucas, Otto, Maximilian, Galicia Garcia, Leticia Elizabeth, Fabig, Gunar, Solimena, Michele, and Weigert, Martin

Abstract

Volume electron microscopy is the method of choice for the in situ interrogation of cellular ultrastructure at the nanometer scale, and with the increase in large raw image datasets generated, improving computational strategies for image segmentation and spatial analysis is necessary. Here we describe a practical and annotation-efficient pipeline for organelle-specific segmentation, spatial analysis and visualization of large volume electron microscopy datasets using freely available, user-friendly software tools that can be run on a single standard workstation. The procedures are aimed at researchers in the life sciences with modest computational expertise, who use volume electron microscopy and need to generate three-dimensional (3D) segmentation labels for different types of cell organelles while minimizing manual annotation efforts, to analyze the spatial interactions between organelle instances and to visualize the 3D segmentation results. We provide detailed guidelines for choosing well-suited segmentation tools for specific cell organelles, and to bridge compatibility issues between freely available open-source tools, we distribute the critical steps as easily installable Album solutions for deep learning segmentation, spatial analysis and 3D rendering. Our detailed description can serve as a reference for similar projects requiring particular strategies for single- or multiple-organelle analysis, which can be achieved with computational resources commonly available to single-user setups.|This protocol provides a pipeline for analyzing volume electron microscopy datasets covering the preparation of raw data, the segmentation of specific organelles, their spatial analysis and three-dimensional visualization of the segmentation maps.The protocol demonstrates the use of tools such as Microscopy Image Browser, ilastik, Labkit and Album, which facilitates the installation of Python-based software (CSBDeep, CellSketch, StarDist, Blender and Jupyter notebooks).|A us

Published
2024
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33. Viral infiltration of pancreatic islets in patients with COVID-19

Author

Steenblock, Charlotte, Richter, Stefanie, Berger, Ilona, Barovic, Marko, Schmid, Janine, Schubert, Undine, Jarzebska, Natalia, von Mässenhausen, Anne, Linkermann, Andreas, Schürmann, Annette, Pablik, Jessica, Dienemann, Thomas, Evert, Katja, Rodionov, Roman N., Semenova, Natalia Y., Zinserling, Vsevolod A., Gainetdinov, Raul R., Baretton, Gustavo, Lindemann, Dirk, Solimena, Michele, Ludwig, Barbara, and Bornstein, Stefan R.

Published
2021
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35. Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes

Author

Khamis, Amna, Canouil, Mickaël, Siddiq, Afshan, Crouch, Hutokshi, Falchi, Mario, Bulow, Manon von, Ehehalt, Florian, Marselli, Lorella, Distler, Marius, Richter, Daniela, Weitz, Jürgen, Bokvist, Krister, Xenarios, Ioannis, Thorens, Bernard, Schulte, Anke M., Ibberson, Mark, Bonnefond, Amelie, Marchetti, Piero, Solimena, Michele, and Froguel, Philippe

Published
2019
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37. Structure, interaction, and nervous connectivity of beta cell primary cilia

Author

Müller, Andreas, primary, Klena, Nikolai, additional, Pang, Song, additional, Galicia Garcia, Leticia Elizabeth, additional, Sulaymankhil, Davud, additional, Topcheva, Oleksandra, additional, Seliskar, Monika, additional, Mziaut, Hassan, additional, Schöniger, Eyke, additional, Friedland, Daniela, additional, Kipke, Nicole, additional, Kretschmar, Susanne, additional, Münster, Carla, additional, Weitz, Jürgen, additional, Distler, Marius, additional, Kurth, Thomas, additional, Schmidt, Deborah, additional, Hess, Harald F., additional, Xu, C. Shan, additional, Pigino, Gaia, additional, and Solimena, Michele, additional

Published
2023
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41. Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes

Author

Ludwig, Barbara, Ludwig, Stefan, Steffen, Anja, Knauf, Yvonne, Zimerman, Baruch, Heinke, Sophie, Lehmann, Susann, Schubert, Undine, Schmid, Janine, Bleyer, Martina, Schönmann, Uwe, Colton, Clark K., Bonifacio, Ezio, Solimena, Michele, Reichel, Andreas, Schally, Andrew V., Rotem, Avi, Barkai, Uriel, Grinberg-Rashi, Helena, Kaup, Franz-Josef, Avni, Yuval, Jones, Peter, and Bornstein, Stefan R.

Published
2017

44. Fostering improved human islet research: a European perspective

Author

Marchetti, Piero, Schulte, Anke M., Marselli, Lorella, Schoniger, Eyke, Bugliani, Marco, Kramer, Werner, Overbergh, Lut, Ullrich, Susanne, Gloyn, Anna L., Ibberson, Mark, Rutter, Guy, Froguel, Philippe, Groop, Leif, McCarthy, Mark I., Dotta, Francesco, Scharfmann, Raphael, Magnan, Christophe, Eizirik, Decio L., Mathieu, Chantal, Cnop, Miriam, Thorens, Bernard, and Solimena, Michele

Published
2019
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46. Content-aware image restoration: pushing the limits of fluorescence microscopy

Author

Weigert, Martin, Schmidt, Uwe, Boothe, Tobias, Müller, Andreas, Dibrov, Alexandr, Jain, Akanksha, Wilhelm, Benjamin, Schmidt, Deborah, Broaddus, Coleman, Culley, Siân, Rocha-Martins, Mauricio, Segovia-Miranda, Fabián, Norden, Caren, Henriques, Ricardo, Zerial, Marino, Solimena, Michele, Rink, Jochen, Tomancak, Pavel, Royer, Loic, Jug, Florian, and Myers, Eugene W.

Published
2018
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48. Gene expression signature predicts rate of type 1 diabetes progression

Author

Suomi, Tomi, primary, Starskaia, Inna, additional, Kalim, Ubaid Ullah, additional, Rasool, Omid, additional, Jaakkola, Maria K., additional, Grönroos, Toni, additional, Välikangas, Tommi, additional, Brorsson, Caroline, additional, Mazzoni, Gianluca, additional, Bruggraber, Sylvaine, additional, Overbergh, Lut, additional, Dunger, David, additional, Peakman, Mark, additional, Chmura, Piotr, additional, Brunak, Søren, additional, Schulte, Anke M., additional, Mathieu, Chantal, additional, Knip, Mikael, additional, Lahesmaa, Riitta, additional, Elo, Laura L., additional, Gillard, Pieter, additional, Casteels, Kristina, additional, Overbergh, Lutgart, additional, Wallace, Chris, additional, Evans, Mark, additional, Thankamony, Ajay, additional, Hendriks, Emile, additional, Marcoveccchio, Loredana, additional, Tree, Timothy, additional, Morgan, Noel G., additional, Richardson, Sarah, additional, Todd, John A., additional, Wicker, Linda, additional, Mander, Adrian, additional, Dayan, Colin, additional, Alhadj Ali, Mohammad, additional, Pieber, Thomas, additional, Eizirik, Decio L., additional, Cnop, Myriam, additional, Pociot, Flemming, additional, Johannesen, Jesper, additional, Rossing, Peter, additional, Quigley, Cristina Legido, additional, Mallone, Roberto, additional, Scharfmann, Raphael, additional, Boitard, Christian, additional, Otonkoski, Timo, additional, Veijola, Riitta, additional, Oresic, Matej, additional, Toppari, Jorma, additional, Danne, Thomas, additional, Ziegler, Anette G., additional, Achenbach, Peter, additional, Rodriguez-Calvo, Teresa, additional, Solimena, Michele, additional, Bonifacio, Ezio E., additional, Speier, Stephan, additional, Holl, Reinhard, additional, Dotta, Francesco, additional, Chiarelli, Francesco, additional, Marchetti, Piero, additional, Bosi, Emanuele, additional, Cianfarani, Stefano, additional, Ciampalini, Paolo, additional, De Beaufort, Carine, additional, Dahl-Jørgensen, Knut, additional, Skrivarhaug, Torild, additional, Joner, Geir, additional, Krogvold, Lars, additional, Jarosz-Chobot, Przemka, additional, Battelino, Tadej, additional, Thorens, Bernard, additional, Gotthardt, Martin, additional, Roep, Bart O., additional, Nikolic, Tanja, additional, Zaldumbide, Arnaud, additional, Lernmark, Ake, additional, Lundgren, Marcus, additional, Costacalde, Guillaume, additional, Strube, Thorsten, additional, Nitsche, Almut, additional, Vela, Jose, additional, Von Herrath, Matthias, additional, Wesley, Johnna, additional, Napolitano-Rosen, Antonella, additional, Thomas, Melissa, additional, Schloot, Nanette, additional, Goldfine, Allison, additional, Waldron-Lynch, Frank, additional, Kompa, Jill, additional, Vedala, Aruna, additional, Hartmann, Nicole, additional, Nicolas, Gwenaelle, additional, van Rampelbergh, Jean, additional, Bovy, Nicolas, additional, Dutta, Sanjoy, additional, Soderberg, Jeannette, additional, Ahmed, Simi, additional, Martin, Frank, additional, Latres, Esther, additional, Agiostratidou, Gina, additional, Koralova, Anne, additional, Willemsen, Ruben, additional, Smith, Anne, additional, Anand, Binu, additional, Datta, Vipan, additional, Puthi, Vijith, additional, Zac-Varghese, Sagen, additional, Dias, Renuka, additional, Sundaram, Premkumar, additional, Vaidya, Bijay, additional, Patterson, Catherine, additional, Owen, Katharine, additional, Piel, Barbara, additional, Heller, Simon, additional, Randell, Tabitha, additional, Gazis, Tasso, additional, Reismen, Elise Bismuth, additional, Carel, Jean-Claude, additional, Riveline, Jean-Pierre, additional, Gautier, Jean-Francoise, additional, Andreelli, Fabrizion, additional, Travert, Florence, additional, Cosson, Emmanuel, additional, Penfornis, Alfred, additional, Petit, Catherine, additional, Feve, Bruno, additional, Lucidarme, Nadine, additional, Beressi, Jean-Paul, additional, Ajzenman, Catherina, additional, Radu, Alina, additional, Greteau-Hamoumou, Stephanie, additional, Bibal, Cecile, additional, Meissner, Thomas, additional, Heidtmann, Bettina, additional, Toni, Sonia, additional, Rami-Merhar, Birgit, additional, Eeckhout, Bart, additional, Peene, Bernard, additional, Vantongerloo, N., additional, Maes, Toon, additional, and Gommers, Leen, additional

Published
2023
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49. Publisher Correction: An open-access volume electron microscopy atlas of whole cells and tissues

Author

Xu, C. Shan, Pang, Song, Shtengel, Gleb, Müller, Andreas, Ritter, Alex T., Hoffman, Huxley K., Takemura, Shin-ya, Lu, Zhiyuan, Pasolli, H. Amalia, Iyer, Nirmala, Chung, Jeeyun, Bennett, Davis, Weigel, Aubrey V., Freeman, Melanie, van Engelenburg, Schuyler B., Walther, Tobias C., Farese, Jr., Robert V., Lippincott-Schwartz, Jennifer, Mellman, Ira, Solimena, Michele, and Hess, Harald F.

Published
2021
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