6533b82efe1ef96bd12927e9

RESEARCH PRODUCT

Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes

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Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells. Fil: Galluzzi, L.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Aaronson, S. A.. Mount Sinai School of Medicine; Estados Unidos Fil: Abrams, J.. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Alnemri, E. S.. Thomas Jefferson University; Estados Unidos Fil: Andrews, D. W.. McMaster University; Canadá Fil: Baehrecke, E. H.. University of Massachussets; Estados Unidos Fil: Bazan, N. G.. Louisiana State University Health Sciences Center; Estados Unidos Fil: Blagosklonny, M. V.. Roswell Park Cancer Institute; Estados Unidos Fil: Blomgren, K.. Universityt of Gothenburg; Suecia. The Queen Silvia Children; Suecia Fil: Borner, C.. Albert-Ludwigs Universität Freiburg; Alemania Fil: Bredesen, E.. Buck Institute for Age Research; Estados Unidos. University of California; Estados Unidos Fil: Brenner, C.. univeristy of Versailles ; Francia Fil: Castedo, M.. Inserm; Francia. Universite Paris Sud; Francia Fil: Cidlowski, J. A.. National Institutes of Health; Estados Unidos Fil: Ciechanover, A.. The Rappaport Faculty of Medicine; Israel Fil: Cohen, G. M.. University of Leicester; Reino Unido Fil: De Laurenzi, V.. Università ‘G. d’Annunzio’ Chieti Pescara; Italia Fil: De Maria, R.. Istituto Superiore di Sanità; Italia. Mediterranean Institute of Oncology; Italia Fil: Deshmukh, M.. University of North Carolina; Estados Unidos Fil: Dynlacht, B. D.. University of New York; Estados Unidos Fil: El Deiry, W. S.. University of Pennsylvania; Estados Unidos Fil: Flavell, R. A.. University of Yale; Estados Unidos Fil: Fulda, S.. University Children; Alemania Fil: Garrido, C.. Inserm; Francia. University of Burgundy; Francia Fil: Golstein, P.. Inserm; Francia. Aix Marseille Université; Francia Fil: Gougeon, M. L.. Instituto Pasteur; Francia Fil: Green, D. R.. St. Jude Children′s Research Hospital; Estados Unidos Fil: Gronemeyer, H.. Institut de Génétique et de Biologie Moléculaire et Cellulaire; Francia. Inserm; Francia Fil: Hajnóczky, G.. Thomas Jefferson University; Estados Unidos Fil: Hardwick, J. M.. Johns Hopkins University; Estados Unidos Fil: Hengartner, M.O.. University Johns Hopkins; Estados Unidos Fil: Ichijo, H.. University of Tokyo; Japón Fil: Jäättelä, M.. Institute of Cancer Biology; Dinamarca Fil: Kepp, O.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Kimchi, A.. Weizmann Institute of Science; Israel Fil: Klionsky, D. J.. University of Michigan; Estados Unidos Fil: Knight, R. A.. University College London; Estados Unidos Fil: Kornbluth, S.. University of Duke; Estados Unidos Fil: Kumar, S.. Hanson Institute; Australia Fil: Levine, B.. Howard Hughes Medical Institute; Estados Unidos. University of Texas; Estados Unidos Fil: Lipton, S. A.. Burnham Institute for Medical Research; Estados Unidos. The Salk Institute for Biological Studies; Estados Unidos. The Scripps Research Institute; Estados Unidos. University of California at San Diego; Estados Unidos Fil: Lugli, E.. National Institutes of Health; Estados Unidos Fil: Madeo, F.. university of Graz; Austria Fil: Malorni, W.. Istituto Superiore di Sanità; Italia Fil: Marine, J. C.. VIB; Bélgica. Ghent University; Bélgica Fil: Martin, S. J.. Trinity College; Irlanda Fil: Medema, J. P.. Academic Medical Center; Países Bajos. University of Amsterdam; Países Bajos Fil: Mehlen, P.. Centre Léon Berard; Francia. Centre National de la Recherche Scientifique; Francia. Universite Lyon 2; Francia Fil: Melino, G.. University of Leicester; Reino Unido. Göttingen Center of Molecular Biosciences; Alemania Fil: Moll, U. M.. Stony Brook University; Estados Unidos. Göttingen Center of Molecular Biosciences; Alemania. University of Göttingen; Alemania Fil: Morselli, E.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Nagata, S.. University of Kyoto; Japón Fil: Nicholson, D. W.. Merck Research Laboratories; Estados Unidos Fil: Nicotera, P.. University of Leicester; Reino Unido Fil: Nuñez, G.. University of Michigan; Estados Unidos Fil: Oren, M.. Weizmann Institute of Science; Israel Fil: Penninger, J.. Institute of Molecular Biotechnology of the Austrian Academy of Science; Austria Fil: Pervaiz, S.. National University of Singapore; Singapur. Duke-NUS Graduate Medical School; Singapur Fil: Peter, M. E.. University of Chicago; Estados Unidos Fil: Piacentini, M.. National Institute for Infectious Diseases IRCCS "L. Spallanzani"; Italia. University of Rome "Tor Vergata"; Italia Fil: Prehn. J. H.. Royal College of Surgeons in Ireland; Irlanda Fil: Puthalakath, H.. La Trobe University; Australia Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Rizzuto, R.. Università di Padova; Italia Fil: Rodrigues, C. M.. Universidade de Lisboa; Portugal Fil: Rubinsztein, D. C.. Cambridge Institute for Medical Research; Reino Unido Fil: Rudel, T.. University of Würzburg; Alemania Fil: Scorrano, L.. University of Geneva ; Suiza. Venetian Institute of Molecular Medicine; Italia Fil: Simon, H. U.. University of Bern; Suiza Fil: Steller, H.. Howard Hughes Medical Institute; Estados Unidos. The Rockefeller University; Estados Unidos Fil: Tschoop, J.. University of Lausanne; Suiza Fil: Tsujimoto, Y.. Osaka University Medical School; Japón Fil: Vandenabeele, P.. Ghent University; Bélgica. VIB; Bélgica Fil: Vitale, I.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Vousden, K. H.. The Beatson Institute for Cancer Research; Reino Unido Fil: Youle, J. R.. National Institutes of Health; Estados Unidos Fil: Yuan, J.. Harvard Medical School; Estados Unidos Fil: Zhivotovsky, B.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Kroemer, G.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia