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4. Editorial Expression of Concern: Cell Lines Derived from Human Parthenogenetic Embryos Can Display Aberrant Centriole Distribution and Altered Expression Levels of Mitotic Spindle Check-point Transcripts

Author

Brevini, Tiziana A. L., Pennarossa, Georgia, Antonini, Stefania, Paffoni, Alessio, Tettamanti, Gianluca, Montemurro, Tiziana, Radaelli, Enrico, Lazzari, Lorenza, Rebulla, Paolo, Scanziani, Eugenio, de Eguileor, Magda, Benvenisty, Nissim, Ragni, Guido, and Gandolfi, Fulvio

Published
2024
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5. ISSCR standards for the use of human stem cells in basic research

Author

Ludwig, Tenneille E., Andrews, Peter W., Barbaric, Ivana, Benvenisty, Nissim, Bhattacharyya, Anita, Crook, Jeremy M., Daheron, Laurence M., Draper, Jonathan S., Healy, Lyn E., Huch, Meritxell, Inamdar, Maneesha S., Jensen, Kim B., Kurtz, Andreas, Lancaster, Madeline A., Liberali, Prisca, Lutolf, Matthias P., Mummery, Christine L., Pera, Martin F., Sato, Yoji, Shimasaki, Noriko, Smith, Austin G., Song, Jihwan, Spits, Claudia, Stacey, Glyn, Wells, Christine A., Zhao, Tongbiao, and Mosher, Jack T.

Published
2023
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8. Why it is important to study human–monkey embryonic chimeras in a dish

Author

De Los Angeles, Alejandro, Regenberg, Alan, Mascetti, Victoria, Benvenisty, Nissim, Church, George, Deng, Hongkui, Izpisua Belmonte, Juan Carlos, Ji, Weizhi, Koplin, Julian, Loh, Yuin-Han, Niu, Yuyu, Pei, Duanqing, Pera, Martin, Pho, Nam, Pinzon-Arteaga, Carlos, Saitou, Mitinori, Silva, Jose C. R., Tao, Tan, Trounson, Alan, Warrier, Tushar, and Zambidis, Elias T.

Published
2022
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9. Ascorbic Acid Ameliorates Molecular and Developmental Defects in Human-Induced Pluripotent Stem Cell and Cerebral Organoid Models of Fragile X Syndrome.

Author

Gunapala, Keith M., Gadban, Aseel, Noreen, Faiza, Schär, Primo, Benvenisty, Nissim, and Taylor, Verdon

Abstract

Fragile X Syndrome (FX) is the most common form of inherited cognitive impairment and falls under the broader category of Autism Spectrum Disorders (ASD). FX is caused by a CGG trinucleotide repeat expansion in the non-coding region of the X-linked Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, leading to its hypermethylation and epigenetic silencing. Animal models of FX rely on the deletion of the Fmr1 gene, which fails to replicate the epigenetic silencing mechanism of the FMR1 gene observed in human patients. Human stem cells carrying FX repeat expansions have provided a better understanding of the basis of epigenetic silencing of FMR1. Previous studies have found that 5-Azacytidine (5Azac) can reverse this methylation; however, 5Azac can be toxic, which may limit its therapeutic potential. Here, we show that the dietary factor Ascorbic Acid (AsA) can reduce DNA methylation in the FMR1 locus and lead to an increase in FMR1 gene expression in FX iPSCs and cerebral organoids. In addition, AsA treatment rescued neuronal gene expression and morphological defects observed in FX iPSC-derived cerebral organoids. Hence, we demonstrate that the dietary co-factor AsA can partially revert the molecular and morphological defects seen in human FX models in vitro. Our findings have implications for the development of novel therapies for FX in the future. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Setting Global Standards for Stem Cell Research and Clinical Translation: The 2016 ISSCR Guidelines.

Author

Daley, George Q, Hyun, Insoo, Apperley, Jane F, Barker, Roger A, Benvenisty, Nissim, Bredenoord, Annelien L, Breuer, Christopher K, Caulfield, Timothy, Cedars, Marcelle I, Frey-Vasconcells, Joyce, Heslop, Helen E, Jin, Ying, Lee, Richard T, McCabe, Christopher, Munsie, Megan, Murry, Charles E, Piantadosi, Steven, Rao, Mahendra, Rooke, Heather M, Sipp, Douglas, Studer, Lorenz, Sugarman, Jeremy, Takahashi, Masayo, Zimmerman, Mark, and Kimmelman, Jonathan

Subjects
Stem Cells, Humans, Informed Consent, Societies, Scientific, Clinical Trials as Topic, Stem Cell Research, Translational Medical Research, EMRO, clinical translation, clinical trials, communication, embryo research, guidelines, stem cells
Abstract

The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006; ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translational, and clinical research. The guidelines demand rigor, oversight, and transparency in all aspects of practice, providing confidence to practitioners and public alike that stem cell science can proceed efficiently and remain responsive to public and patient interests. Here, we highlight key elements and recommendations in the guidelines and summarize the recommendations and deliberations behind them.

Published
2016

16. ISSCR standards for the use of human stem cells in basic research

Author

Ludwig, Tenneille E., Andrews, Peter W., Barbaric, Ivana, Benvenisty, Nissim, Bhattacharyya, Anita, Crook, Jeremy M., Daheron, Laurence M., Draper, Jonathan S., Healy, Lyn E., Huch, Meritxell, Inamdar, Maneesha S., Jensen, Kim B., Kurtz, Andreas, Lancaster, Madeline A., Liberali, Prisca, Lutolf, Matthias P, Mummery, Christine L., Pera, Martin F., Sato, Yoji, Shimasaki, Noriko, Smith, Austin G., Song, Jihwan, Spits, Claudia, Stacey, Glyn, Wells, Christine A., Zhao, Tongbiao, Mosher, Jack T., Ludwig, Tenneille E., Andrews, Peter W., Barbaric, Ivana, Benvenisty, Nissim, Bhattacharyya, Anita, Crook, Jeremy M., Daheron, Laurence M., Draper, Jonathan S., Healy, Lyn E., Huch, Meritxell, Inamdar, Maneesha S., Jensen, Kim B., Kurtz, Andreas, Lancaster, Madeline A., Liberali, Prisca, Lutolf, Matthias P, Mummery, Christine L., Pera, Martin F., Sato, Yoji, Shimasaki, Noriko, Smith, Austin G., Song, Jihwan, Spits, Claudia, Stacey, Glyn, Wells, Christine A., Zhao, Tongbiao, and Mosher, Jack T.

Abstract

The laboratory culture of human stem cells seeks to capture a cellular state as an in vitro surrogate of a biological system. For the results and outputs from this research to be accurate, meaning-ful, and durable, standards that ensure reproducibility and reli-ability of the data should be applied. Although such standards have been previously proposed for repositories and distribution centers, no widely accepted best practices exist for laboratory research with human pluripotent and tissue stem cells. To fill that void, the International Society for Stem Cell Research has developed a set of recommendations, including reporting criteria, for scientists in basic research laboratories. These criteria are de-signed to be technically and financially feasible and, when imple-mented, enhance the reproducibility and rigor of stem cell research.

Published
2024
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17. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders

Author

Brennand, Kristen J, Marchetto, M Carol, Benvenisty, Nissim, Brüstle, Oliver, Ebert, Allison, Belmonte, Juan Carlos Izpisua, Kaykas, Ajamete, Lancaster, Madeline A, Livesey, Frederick J, McConnell, Michael J, McKay, Ronald D, Morrow, Eric M, Muotri, Alysson R, Panchision, David M, Rubin, Lee L, Sawa, Akira, Soldner, Frank, Song, Hongjun, Studer, Lorenz, Temple, Sally, Vaccarino, Flora M, Wu, Jun, Vanderhaeghen, Pierre, Gage, Fred H, and Jaenisch, Rudolf

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurosciences, Neurological, Brain, Brain Diseases, Drug Discovery, Humans, Induced Pluripotent Stem Cells, Mosaicism, Neurogenesis, Precision Medicine, Clinical Sciences, Biochemistry and cell biology
Abstract

As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

Published
2015

21. Genomic Imprinting and Physiological Processes in Mammals

Author

Tucci, Valter, Bartolomei, Marisa S., Benvenisty, Nissim, Bourc’his, Déborah, Charalambous, Marika, Dulac, Catherine, Feil, Robert, Glaser, Juliane, Huelsmann, Lisa, John, Rosalind M., McNamara, Gráinne I., Moorwood, Kim, Muscatelli, Francoise, Sasaki, Hiroyuki, Strassmann, Beverly I., Vincenz, Claudius, Wilkins, Jon, Isles, Anthony R., Kelsey, Gavin, and Ferguson-Smith, Anne C.

Published
2019
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46. Derivation and differentiation of haploid human embryonic stem cells

Author

Sagi, Ido, Chia, Gloryn, Golan-Lev, Tamar, Peretz, Mordecai, Weissbein, Uri, Sui, Lina, Sauer, Mark V., Yanuka, Ofra, Egli, Dieter, and Benvenisty, Nissim

Subjects
Physiological aspects, Research, Embryonic stem cells -- Physiological aspects, Cell differentiation -- Research, Haploidy -- Research, Cytological research, Cell research
Abstract

Haploid genetics is useful for delineating genome function. Although haploid genetics has been mostly restricted to unicellular organisms, recent reports of haploid ES cells have extended it into animal species, [...], Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to ensure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species (1-6), but haploid human ES cells have yet to be reported. Here we generated and analysed a collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics, such as self-renewal capacity and a pluripotency-specific molecular signature. Moreover, we demonstrated the utility of these cells as a platform for loss-of-function genetic screening. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and of genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Surprisingly, we found that a haploid human genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers both in vitro and in vivo, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics and development.

Published
2016

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