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18 results on '"Zaghi, Mattia"'

1. SETD5 haploinsufficiency affects mitochondrial compartment in neural cells.

Author

Zaghi, Mattia, Longo, Fabiana, Massimino, Luca, Rubio, Alicia, Bido, Simone, Mazzara, Pietro Giuseppe, Bellini, Edoardo, Banfi, Federica, Podini, Paola, Maltecca, Francesca, Zippo, Alessio, Broccoli, Vania, and Sessa, Alessandro

Subjects
Neurons, Chromatin, Mitochondria, Animals, Humans, Mice, Methyltransferases, Haploinsufficiency, Neural Stem Cells, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Nonembryonic - Non-Human, Neurosciences, Genetics, Stem Cell Research, Aetiology, 2.1 Biological and endogenous factors, Neurological, Clinical Sciences
Abstract

BackgroundNeurodevelopmental disorders (NDDs) are heterogeneous conditions due to alterations of a variety of molecular mechanisms and cell dysfunctions. SETD5 haploinsufficiency leads to NDDs due to chromatin defects. Epigenetic basis of NDDs has been reported in an increasing number of cases while mitochondrial dysfunctions are more common within NDD patients than in the general population.MethodsWe investigated in vitro neural stem cells as well as the brain of the Setd5 haploinsufficiency mouse model interrogating its transcriptome, analyzing mitochondrial structure, biochemical composition, and dynamics, as well as mitochondrial functionality.ResultsMitochondrial impairment is facilitated by transcriptional aberrations originated by the decrease of the SETD5 enzyme. Low levels of SETD5 resulted in fragmented mitochondria, reduced mitochondrial membrane potential, and ATP production both in neural precursors and neurons. Mitochondria were also mislocalized in mutant neurons, with reduced organelles within neurites and synapses.LimitationsWe found several defects in the mitochondrial compartment; however, we can only speculate about their position in the hierarchy of the pathological mechanisms at the basis of the disease.ConclusionsOur study explores the interplay between chromatin regulation and mitochondria functions as a possible important aspect of SETD5-associated NDD pathophysiology. Our data, if confirmed in patient context, suggest that the mitochondrial activity and dynamics may represent new therapeutic targets for disorders associated with the loss of SETD5.

Published
2023

2. First-hit SETBP1 mutations cause a myeloproliferative disorder with bone marrow fibrosis

Author

Crespiatico, Ilaria, Zaghi, Mattia, Mastini, Cristina, D’Aliberti, Deborah, Mauri, Mario, Mercado, Carl Mirko, Fontana, Diletta, Spinelli, Silvia, Crippa, Valentina, Inzoli, Elena, Manghisi, Beatrice, Civettini, Ivan, Ramazzotti, Daniele, Sangiorgio, Valentina, Gengotti, Michele, Brambilla, Virginia, Aroldi, Andrea, Banfi, Federica, Barone, Cristiana, Orsenigo, Roberto, Riera, Ludovica, Riminucci, Mara, Corsi, Alessandro, Breccia, Massimo, Morotti, Alessandro, Cilloni, Daniela, Roccaro, Aldo, Sacco, Antonio, Stagno, Fabio, Serafini, Marta, Mottadelli, Federica, Cazzaniga, Giovanni, Pagni, Fabio, Chiarle, Roberto, Azzoni, Emanuele, Sessa, Alessandro, Gambacorti-Passerini, Carlo, Elli, Elena Maria, Mologni, Luca, and Piazza, Rocco

Published
2024
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6. Frataxin gene editing rescues Friedreich’s ataxia pathology in dorsal root ganglia organoid-derived sensory neurons

Author

Mazzara, Pietro Giuseppe, Muggeo, Sharon, Luoni, Mirko, Massimino, Luca, Zaghi, Mattia, Valverde, Parisa Tajalli-Tehrani, Brusco, Simone, Marzi, Matteo Jacopo, Palma, Cecilia, Colasante, Gaia, Iannielli, Angelo, Paulis, Marianna, Cordiglieri, Chiara, Giannelli, Serena Gea, Podini, Paola, Gellera, Cinzia, Taroni, Franco, Nicassio, Francesco, Rasponi, Marco, and Broccoli, Vania

Published
2020
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7. Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition

Author

Zaghi, Mattia, primary, Banfi, Federica, additional, Massimino, Luca, additional, Volpin, Monica, additional, Bellini, Edoardo, additional, Brusco, Simone, additional, Merelli, Ivan, additional, Barone, Cristiana, additional, Bruni, Michela, additional, Bossini, Linda, additional, Lamparelli, Luigi Antonio, additional, Pintado, Laura, additional, D’Aliberti, Deborah, additional, Spinelli, Silvia, additional, Mologni, Luca, additional, Colasante, Gaia, additional, Ungaro, Federica, additional, Cioni, Jean-Michel, additional, Azzoni, Emanuele, additional, Piazza, Rocco, additional, Montini, Eugenio, additional, Broccoli, Vania, additional, and Sessa, Alessandro, additional

Published
2023
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9. Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition

Author

Zaghi, M, Banfi, F, Massimino, L, Volpin, M, Bellini, E, Brusco, S, Merelli, I, Barone, C, Bruni, M, Bossini, L, Lamparelli, L, Pintado, L, D'Aliberti, D, Spinelli, S, Mologni, L, Colasante, G, Ungaro, F, Cioni, J, Azzoni, E, Piazza, R, Montini, E, Broccoli, V, Sessa, A, Zaghi, Mattia, Banfi, Federica, Massimino, Luca, Volpin, Monica, Bellini, Edoardo, Brusco, Simone, Merelli, Ivan, Barone, Cristiana, Bruni, Michela, Bossini, Linda, Lamparelli, Luigi Antonio, Pintado, Laura, D'Aliberti, Deborah, Spinelli, Silvia, Mologni, Luca, Colasante, Gaia, Ungaro, Federica, Cioni, Jean-Michel, Azzoni, Emanuele, Piazza, Rocco, Montini, Eugenio, Broccoli, Vania, Sessa, Alessandro, Zaghi, M, Banfi, F, Massimino, L, Volpin, M, Bellini, E, Brusco, S, Merelli, I, Barone, C, Bruni, M, Bossini, L, Lamparelli, L, Pintado, L, D'Aliberti, D, Spinelli, S, Mologni, L, Colasante, G, Ungaro, F, Cioni, J, Azzoni, E, Piazza, R, Montini, E, Broccoli, V, Sessa, A, Zaghi, Mattia, Banfi, Federica, Massimino, Luca, Volpin, Monica, Bellini, Edoardo, Brusco, Simone, Merelli, Ivan, Barone, Cristiana, Bruni, Michela, Bossini, Linda, Lamparelli, Luigi Antonio, Pintado, Laura, D'Aliberti, Deborah, Spinelli, Silvia, Mologni, Luca, Colasante, Gaia, Ungaro, Federica, Cioni, Jean-Michel, Azzoni, Emanuele, Piazza, Rocco, Montini, Eugenio, Broccoli, Vania, and Sessa, Alessandro

Abstract

Within the chromatin, distal elements interact with promoters to regulate specific transcriptional programs. Histone acetylation, interfering with the net charges of the nucleosomes, is a key player in this regulation. Here, we report that the oncoprotein SET is a critical determinant for the levels of histone acetylation within enhancers. We disclose that a condition in which SET is accumulated, the severe Schinzel-Giedion Syndrome (SGS), is characterized by a failure in the usage of the distal regulatory regions typically employed during fate commitment. This is accompanied by the usage of alternative enhancers leading to a massive rewiring of the distal control of the gene transcription. This represents a (mal)adaptive mechanism that, on one side, allows to achieve a certain degree of differentiation, while on the other affects the fine and corrected maturation of the cells. Thus, we propose the differential in cis-regulation as a contributing factor to the pathological basis of SGS and possibly other the SET-related disorders in humans.

Published
2023

11. Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition

Author

Zaghi Mattia, Federica Banfi, Luca Massimino, Monica Volpin, Edoardo Bellini, Simone Brusco, Ivan Merelli, Cristiana Barone, Michela Bruni, Linda Bossini, Luigi Antonio Lamparelli, Laura Pintado, Deborah D’Aliberti, Silvia Spinelli, Luca Mologni, Gaia Colasante, Federica Ungaro, Jean-Michel Cioni, Emanuele Azzoni, Rocco Piazza, Eugenio Montini, Vania Broccoli, Alessandro Sessa, Zaghi, M, Banfi, F, Massimino, L, Volpin, M, Bellini, E, Brusco, S, Merelli, I, Barone, C, Bruni, M, Bossini, L, Lamparelli, L, Pintado, L, D'Aliberti, D, Spinelli, S, Mologni, L, Colasante, G, Ungaro, F, Cioni, J, Azzoni, E, Piazza, R, Montini, E, Broccoli, V, and Sessa, A

Subjects
cell differentiation, Schinzel-Gedion syndrome, chromatin, genetic, gene regulation, SET
Abstract

SUMMARYWithin the chromatin, distal elements interact with promoters to regulate specific transcriptional programs. Histone acetylation, interfering with the net charges of the nucleosomes, is a key player in this regulation. Here, we report that the onco-protein SET is a critical determinant for the levels of histone acetylation within enhancers. We disclose that conditions in which SET is accumulated, including the severe Schinzel-Giedion Syndrome (SGS), are characterized by a failure in the usage of the distal regulatory regions typically employed during fate commitment. This is accompanied by the usage of alternative enhancers leading to a massive rewiring of the distal control of the gene transcription. This represents a (mal)adaptive mechanism that, on one side, allows to achieve a certain degree of differentiation, while on the other affects the fine and corrected maturation of the cells. Thus, we propose the differential in cis-regulation as a contributing factor to the pathological basis of the SET-related disorders in humans, including SGS, neurodevelopmental disorders, myeloproliferative diseases, and cancer.

Published
2022
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12. A SOX2-engineered epigenetic silencer factor represses the glioblastoma genetic program and restrains tumor development

Author

Benedetti, Valerio, Banfi, Federica, Zaghi, Mattia, Moll-Diaz, Raquel, Massimino, Luca, Argelich, Laura, Bellini, Edoardo, Bido, Simone, Muggeo, Sharon, Ordazzo, Gabriele, Mastrototaro, Giuseppina, Moneta, Matteo, Sessa, Alessandro, and Broccoli, Vania

Subjects
Mice, Multidisciplinary, Brain Neoplasms, Cell Line, Tumor, SOXB1 Transcription Factors, Neoplastic Stem Cells, Animals, Humans, Glioma, Glioblastoma, Epigenesis, Genetic
Abstract

Current therapies remain unsatisfactory in preventing the recurrence of glioblastoma multiforme (GBM), which leads to poor patient survival. By rational engineering of the transcription factor SOX2, a key promoter of GBM malignancy, together with the Kruppel-associated box and DNA methyltransferase3A/L catalytic domains, we generated a synthetic repressor named SOX2 epigenetic silencer (SES), which induces the transcriptional silencing of its original targets. By doing so, SES kills both glioma cell lines and patient-derived cancer stem cells in vitro and in vivo. SES expression, through local viral delivery in mouse xenografts, induces strong regression of human tumors and survival rescue. Conversely, SES is not harmful to neurons and glia, also thanks to a minimal promoter that restricts its expression in mitotically active cells, rarely present in the brain parenchyma. Collectively, SES produces a significant silencing of a large fraction of the SOX2 transcriptional network, achieving high levels of efficacy in repressing aggressive brain tumors.

Published
2022
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14. Contributors

Author

Araki, Yasuto, Beristain-Pozos, Juan Daniel, Bhadra, Mridula, Bhebhe, Arnold, Bisht, Deepa, Burton, Mark, Castro-Morales, Diana, Chen, Pao-Yang, Climent, Montserrat, Colón-Caraballo, Mariano, Coppedè, Fabio, Cozma, Angela, Davey, Matthew G., Dugué, Pierre-Antoine, Edwards, Dean P., El-Awady, Raafat, El-Heis, Sarah, Elia, Leonardo, Eriksson, Johan G., Farina, Floriana Maria, Flores-Caldera, Idhaliz, Fodor, Adriana, Fuso, Andrea, Godfrey, Keith M., Gomez-Verjan, Juan Carlos, Grill, Jacques, Gupta, Manish Kumar, Hall, Ignacio Fernando, Hedrich, Christian Michael, Hopper, John L., Hoyo, Cathrine, Huang, Shixia, Huang, Yu-Chun, Karmaus, Wilfried, Katsardis, Charis, Kong, Dewei, Kowluru, Anjaneyulu, Kowluru, Renu A., Li, Shuai, Lillycrop, Karen A., Lim, Lillian Yuxian, Lin, Guan-Jun, Lin, Pei-Yu, Løkhammer, Solveig, Lyra Sheu, Chiao-Yu, Mahnke, Amanda H., Mastrototaro, Giuseppina, McConkey, Haley, Meyering, Shabana S., Miller, Nicola, Milne, Roger L., Mimura, Toshihide, Minarovits, Janos, Miranda, Rajesh C., Mohan, Vasavi, Mohiuddin, Mohammed Khaliq, Mukherjee, Nandini, Mutirangura, Apiwat, Niller, Hans Helmut, Pagiatakis, Christina, Papamichael, Maria Michelle, Park, Sarah S., Perales, Selene G., Pruksananonda, Kamthorn, Rajasingh, Johnson, Rajasingh, Sheeja, Ramadan, Wafaa S.H., Rivero-Segura, Nadia Alejandra, Roman, Gabriela, Rouleau, Etienne, Rousseau, Léa Guerrini, Rouzer, Siara K., Rusu, Adriana, Saber-Ayad, Maha M., Sachan, Manisha, Sadikovic, Bekim, Saldanha, Sabita N., Salem, Nihal A., Sandoval-Rodríguez, Francisco Ernesto, Sassi, Hela, Seow, Wei Qiang, Sessa, Alessandro, Sharma, Nikita, Shi, Zhongcheng, Sitar-Taut, Adela, Skaar, David, Suharoschi, Ramona, Teo, Adrian Kee Keong, Thumoju, Sravya, Tint, Mya Thway, Tollefsbol, Trygve O., Tseng, Alexander M., Vulturar, Romana, Wang, Xuan, Wasinarom, Artisa, Watson, Erica D., Young, Nicolas L., Zhou, Zhigang, Zaghi, Mattia, and Ziyab, Ali H.

Published
2024
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15. First-Hit SETBP1 Mutations Cause a Myeloproliferative Disorder with Bone Marrow Fibrosis

Author

Crespiatico, Ilaria, Zaghi, Mattia, Mastini, Cristina, D'Aliberti, Deborah, Mauri, Mario, Mercado, Carl Mirko, Fontana, Diletta, Spinelli, Silvia, Crippa, Valentina, Inzoli, Elena, Manghisi, Beatrice, Civettini, Ivan, Ramazzotti, Daniele, Lavoro, Valentina Fabiola Ilenia, Gengotti, Michele, Brambilla, Virginia, Aroldi, Andrea, Banfi, Federica, Barone, Cristiana, Orsenigo, Roberto, Riera, Ludovica, Riminucci, Mara, Corsi, Alessandro, Breccia, Massimo, Morotti, Alessandro, Cilloni, Daniela, Roccaro, Aldo, Sacco, Antonio, Stagno, Fabio, Serafini, Marta, Mottadelli, Federica, Cazzaniga, Giovanni, Pagni, Fabio, Chiarle, Roberto, Azzoni, Emanuele, Sessa, Alessandro, Gambacorti-Passerini, Carlo, Elli, Elena Maria, Mologni, Luca, and Piazza, Rocco

Published
2023
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16. TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway

Author

Mastrototaro, Giuseppina, primary, Zaghi, Mattia, additional, Massimino, Luca, additional, Moneta, Matteo, additional, Mohammadi, Neda, additional, Banfi, Federica, additional, Bellini, Edoardo, additional, Indrigo, Marzia, additional, Fagnocchi, Giulia, additional, Bagliani, Anna, additional, Taverna, Stefano, additional, Rohm, Maria, additional, Herzig, Stephan, additional, and Sessa, Alessandro, additional

Published
2021
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18. First-hit SETBP1mutations cause a myeloproliferative disorder with bone marrow fibrosis

Author

Crespiatico, Ilaria, Zaghi, Mattia, Mastini, Cristina, D’Aliberti, Deborah, Mauri, Mario, Mercado, Carl Mirko, Fontana, Diletta, Spinelli, Silvia, Crippa, Valentina, Inzoli, Elena, Manghisi, Beatrice, Civettini, Ivan, Ramazzotti, Daniele, Sangiorgio, Valentina, Gengotti, Michele, Brambilla, Virginia, Aroldi, Andrea, Banfi, Federica, Barone, Cristiana, Orsenigo, Roberto, Riera, Ludovica, Riminucci, Mara, Corsi, Alessandro, Breccia, Massimo, Morotti, Alessandro, Cilloni, Daniela, Roccaro, Aldo, Sacco, Antonio, Stagno, Fabio, Serafini, Marta, Mottadelli, Federica, Cazzaniga, Giovanni, Pagni, Fabio, Chiarle, Roberto, Azzoni, Emanuele, Sessa, Alessandro, Gambacorti-Passerini, Carlo, Elli, Elena Maria, Mologni, Luca, and Piazza, Rocco

Abstract

•SETBP1mutations, acting as a first-hit/early event, drive an aggressive myelofibrosis-like myeloproliferative disorder.•SETBP1mutations discriminate between 2 subtypes of triple-negative myelofibrosis, with different genetic landscape and aggressiveness.

Published
2024
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