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12 results on '"Aguilera-Castrejon A"'

3. Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs

Author

Tarazi, Shadi, primary, Aguilera-Castrejon, Alejandro, additional, Joubran, Carine, additional, Ghanem, Nadir, additional, Ashouokhi, Shahd, additional, Roncato, Francesco, additional, Wildschutz, Emilie, additional, Haddad, Montaser, additional, Oldak, Bernardo, additional, Gomez-Cesar, Elidet, additional, Livnat, Nir, additional, Viukov, Sergey, additional, Lokshtanov, Dmitry, additional, Naveh-Tassa, Segev, additional, Rose, Max, additional, Hanna, Suhair, additional, Raanan, Calanit, additional, Brenner, Ori, additional, Kedmi, Merav, additional, Keren-Shaul, Hadas, additional, Lapidot, Tsvee, additional, Maza, Itay, additional, Novershtern, Noa, additional, and Hanna, Jacob H., additional

Published
2022
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4. Recent insights into mammalian natural and synthetic ex utero embryogenesis

Author

Bernardo Oldak, Alejandro Aguilera-Castrejon, and Jacob H Hanna

Subjects
Mice, Organogenesis, Genetics, Humans, Animals, Embryonic Development, Rodentia, Embryo Implantation, Embryo, Mammalian, Developmental Biology
Abstract

Research on early postimplantation mammalian development has been limited by the small size and intrauterine confinement of the developing embryos. Owing to the inability to observe and manipulate living embryos at these stages in utero, the establishment of robust ex utero embryo-culture systems that capture prolonged periods of mouse development has been an important research goal. In the last few years, these methods have been significantly improved by the optimization and enhancement of in vitro culture systems sustaining embryo development during peri-implantation stages for several species, and more recently, proper growth of natural mouse embryos from pregastrulation to late organogenesis stages and of embryonic stem cell (ES)-derived synthetic embryo models until early organogenesis stages. Here, we discuss the most recent ex utero embryo-culture systems established to date for rodents, nonhuman primates, and humans. We emphasize their technical aspects and developmental timeframe and provide insights into the new opportunities that these methods will contribute to the study of natural and synthetic mammalian embryogenesis and the stem-cell field.

Published
2022

5. SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity

Author

Sheban, Daoud, primary, Shani, Tom, additional, Maor, Roey, additional, Aguilera-Castrejon, Alejandro, additional, Mor, Nofar, additional, Oldak, Bernardo, additional, Shmueli, Merav D., additional, Eisenberg-Lerner, Avital, additional, Bayerl, Jonathan, additional, Hebert, Jakob, additional, Viukov, Sergey, additional, Chen, Guoyun, additional, Kacen, Assaf, additional, Krupalnik, Vladislav, additional, Chugaeva, Valeriya, additional, Tarazi, Shadi, additional, Rodríguez-delaRosa, Alejandra, additional, Zerbib, Mirie, additional, Ulman, Adi, additional, Masarwi, Solaiman, additional, Kupervaser, Meital, additional, Levin, Yishai, additional, Shema, Efrat, additional, David, Yael, additional, Novershtern, Noa, additional, Hanna, Jacob H., additional, and Merbl, Yifat, additional

Published
2022
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6. Principles of signaling pathway modulation for enhancing human naive pluripotency induction

Author

Bayerl, Jonathan, primary, Ayyash, Muneef, additional, Shani, Tom, additional, Manor, Yair Shlomo, additional, Gafni, Ohad, additional, Massarwa, Rada, additional, Kalma, Yael, additional, Aguilera-Castrejon, Alejandro, additional, Zerbib, Mirie, additional, Amir, Hadar, additional, Sheban, Daoud, additional, Geula, Shay, additional, Mor, Nofar, additional, Weinberger, Leehee, additional, Naveh Tassa, Segev, additional, Krupalnik, Vladislav, additional, Oldak, Bernardo, additional, Livnat, Nir, additional, Tarazi, Shadi, additional, Tawil, Shadi, additional, Wildschutz, Emilie, additional, Ashouokhi, Shahd, additional, Lasman, Lior, additional, Rotter, Varda, additional, Hanna, Suhair, additional, Ben-Yosef, Dalit, additional, Novershtern, Noa, additional, Viukov, Sergey, additional, and Hanna, Jacob H., additional

Published
2021
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7. The Molecular and Functional Foundations of Conducive Somatic Cell Reprogramming to Ground State Pluripotency

Author

Itay Maza, Yair S. Manor, Nofar Mor, Vladislav Krupalnik, Sergey Viukov, Hila Gingold, Jacob H. Hanna, Rada Massarwa, Roberta Scognamiglio, Awni Mousa, Hadas Hezroni, Sima Benjamin, Yoach Rais, Alejandro Aguilera-Castrejon, Daoud Sheban, Noa Novershtern, Shlomit Gilad, Andreas Trumpp, Diego Jaitin, Asaf Zviran, Mirie Zerbib, Yonatan Stelzer, Elad Chomsky, Leehee Weinberger, Shani Peles, Suhair Hanna, David Larastiaso, Yitzhak Pilpel, William J. Greenleaf, Igor Ulitsky, Muneef Ayyash, Ohad Gafni, Jonathan Bayerl, Jason D. Buenrostro, Amos Tanay, and Ido Amit

Subjects
DNA methylation, biology.protein, RNA polymerase II, Epigenetics, Biology, Cell fate determination, Enhancer, Induced pluripotent stem cell, Reprogramming, Chromatin, Cell biology
Abstract

The epigenetic dynamics of iPSC reprogramming in correctly reprogrammed cells at high resolution and throughout the entire process, remain largely undefined. This gap in understanding results from the inefficiency of conventional reprogramming methods coupled with the difficulty of prospectively isolating the rare cells that eventually correctly reprogram into iPSCs. Here we characterize cell fate conversion from fibroblast to iPSC using radically efficient murine reprogramming systems. This comprehensive characterization provides single day resolution of dynamic changes in levels of gene expression, chromatin modifications, TF binding, DNA accessibility and DNA methylation. The integrative analysis identified two transcriptional modules that dominate successful reprogramming. One consists of genes whose transcription is regulated by on/off epigenetic switching of modifications in their promoters (abbreviated as ESPGs), and the second consists of genes with promoters in a constitutively active chromatin state, but a dynamic expression pattern (abbreviated as CAPGs). ESPGs are mainly regulated by OSK, rather than Myc, and are enriched for cell fate determinants and pluripotency factors. We used the ESPG module to study the identity and temporal occurrence of activating and repressing epigenetic switching during reprogramming. Removal of repressive chromatin modifications precedes chromatin opening and binding of RNA polymerase II at enhancers and promoters, and the opposite dynamics occur during repression of enhancers and promoters. Genome wide DNA methylation analysis identified a group of super-enhancers targeted by OSK, whose early demethylation definitively marks commitment to a successful reprogramming trajectory also in inefficient conventional reprogramming systems. CAPGs are predominantly regulated by Myc rather than OSK and are enriched for cell biosynthetic regulatory functions. CAPGs are distinctively regulated by multiple synergetic ways: 1) Myc activity, delivered either endogenously or exogenously, dominates CAPG expression changes and is indispensable for induction of pluripotency in somatic cells; 2) A change in tRNA codon usage which is specific to Myc regulated CAPGs, but not ESPGs, and favors their translation. In summary, our unbiased high-resolution mapping of epigenetic changes on somatic cells that are committed to undergo successful reprogramming reveals interleaved epigenetic and Myc governed biosynthetic reconfigurations that rapidly commission and propel conducive reprogramming toward naive pluripotency.

Published
2018

8. Neutralizing Gatad2a-Chd4-Mbd3 Axis within the NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency

Author

Krupalnik, Dalia Elinger, Hagit Masika, Elad Chomsky, Sergey Viukov, Jacob H. Hanna, Shay Geula, Daoud Sheban, Miguel A. Esteban, Alejandro Aguilera-Castrejon, William J. Greenleaf, Noa Novershtern, Yoach Rais, Nofar Mor, Ohad Gafni, Suhair Hanna, Yishai Levin, Tom Shani, Shani Peles, Jonathan Bayerl, Lior Lasman, Jason D. Buenrostro, Asaf Zviran, Yifat Merbl, Mirie Zerbib, Rada Massarwa, Yehudit Bergman, and Tzachi Hagai

Subjects
Somatic cell, Cellular differentiation, Context (language use), CHD4, Biology, Induced pluripotent stem cell, Reprogramming, Mi-2/NuRD complex, Phenotype, Cell biology
Abstract

The Nucleosome Remodeling and Deacytelase (NuRD) complex is a co-repressive complex involved in many pathological and physiological processes in the cell. Previous studies have identified one of its components, Mbd3, as a potent inhibitor for reprogramming of somatic cells to pluripotency. Following OSKM induction, early and partial depletion of Mbd3 protein followed by applying naïve ground-state pluripotency conditions, results in a highly efficient and near-deterministic generation of mouse iPS cells. Increasing evidence indicates that the NuRD complex assumes multiple mutually exclusive protein complexes, and it remains unclear whether the deterministic iPSC phenotype is the result of a specific NuRD sub complex. Since complete ablation of Mbd3 blocks somatic cell proliferation, here we aimed to identify alternative ways to block Mbd3-dependent NuRD activity by identifying additional functionally relevant components of the Mbd3/NuRD complex during early stages of reprogramming. We identified Gatad2a (also known as P66α), a relatively uncharacterized NuRD-specific subunit, whose complete deletion does not impact somatic cell proliferation, yet specifically disrupts Mbd3/NuRD repressive activity on the pluripotency circuit during both stem cell differentiation and reprogramming to pluripotency. Complete ablation of Gatad2a in somatic cells, but not Gatad2b, results in a deterministic naïve iPSC reprogramming where up to 100% of donor somatic cells successfully complete the process within 8 days. Genetic and biochemical analysis established a distinct sub-complex within the NuRD complex (Gatad2a-Chd4-Mbd3) as the functional and biochemical axis blocking reestablishment of murine naïve pluripotency. Disassembly of this axis by depletion of Gatad2a, results in resistance to conditions promoting exit of naïve pluripotency and delays differentiation. We further highlight context- and posttranslational dependent modifications of the NuRD complex affecting its interactions and assembly in different cell states. Collectively, our work unveils the distinct functionality, composition and interactions of Gatad2a-Chd4-Mbd3/NuRD subcomplex during the resolution and establishment of mouse naïve pluripotency.

Published
2018

9. Deterministic Somatic Cell Reprogramming Involves Continuous Transcriptional Changes Governed by Myc and Epigenetic-Driven Modules

Author

Zviran, Asaf, primary, Mor, Nofar, additional, Rais, Yoach, additional, Gingold, Hila, additional, Peles, Shani, additional, Chomsky, Elad, additional, Viukov, Sergey, additional, Buenrostro, Jason D., additional, Scognamiglio, Roberta, additional, Weinberger, Leehee, additional, Manor, Yair S., additional, Krupalnik, Vladislav, additional, Zerbib, Mirie, additional, Hezroni, Hadas, additional, Jaitin, Diego Adhemar, additional, Larastiaso, David, additional, Gilad, Shlomit, additional, Benjamin, Sima, additional, Gafni, Ohad, additional, Mousa, Awni, additional, Ayyash, Muneef, additional, Sheban, Daoud, additional, Bayerl, Jonathan, additional, Aguilera-Castrejon, Alejandro, additional, Massarwa, Rada, additional, Maza, Itay, additional, Hanna, Suhair, additional, Stelzer, Yonatan, additional, Ulitsky, Igor, additional, Greenleaf, William J., additional, Tanay, Amos, additional, Trumpp, Andreas, additional, Amit, Ido, additional, Pilpel, Yitzhak, additional, Novershtern, Noa, additional, and Hanna, Jacob H., additional

Published
2019
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10. Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency

Author

Mor, Nofar, primary, Rais, Yoach, additional, Sheban, Daoud, additional, Peles, Shani, additional, Aguilera-Castrejon, Alejandro, additional, Zviran, Asaf, additional, Elinger, Dalia, additional, Viukov, Sergey, additional, Geula, Shay, additional, Krupalnik, Vladislav, additional, Zerbib, Mirie, additional, Chomsky, Elad, additional, Lasman, Lior, additional, Shani, Tom, additional, Bayerl, Jonathan, additional, Gafni, Ohad, additional, Hanna, Suhair, additional, Buenrostro, Jason D., additional, Hagai, Tzachi, additional, Masika, Hagit, additional, Vainorius, Gintautas, additional, Bergman, Yehudit, additional, Greenleaf, William J., additional, Esteban, Miguel A., additional, Elling, Ulrich, additional, Levin, Yishai, additional, Massarwa, Rada, additional, Merbl, Yifat, additional, Novershtern, Noa, additional, and Hanna, Jacob H., additional

Published
2018
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11. Neutralizing Gatad2a-Chd4-Mbd3 Axis within the NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency

Author

Mor, Nofar, primary, Rais, Yoach, additional, Peles, Shani, additional, Sheban, Daoud, additional, Aguilera-Castrejon, Alejandro, additional, Zviran, Asaf, additional, Elinger, Dalia, additional, Viukov, Sergey, additional, Geula, Shay, additional, Krupalnik, Vladislav, additional, Zerbib, Mirie, additional, Chomsky, Elad, additional, Lasman, Lior, additional, Shani, Tom, additional, Bayerl, Jonathan, additional, Gafni, Ohad, additional, Hanna, Suhair, additional, Buenrostro, Jason D., additional, Hagai, Tzachi, additional, Masika, Hagit, additional, Bergman, Yehudit, additional, Greenleaf, William J., additional, Esteban, Miguel A., additional, Levin, Yishai, additional, Massarwa, Rada, additional, Merbl, Yifat, additional, Novershtern, Noa, additional, and Hanna, Jacob H., additional

Published
2018
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12. The Molecular and Functional Foundations of Conducive Somatic Cell Reprogramming to Ground State Pluripotency

Author

Zviran, Asaf, primary, Mor, Nofar, additional, Rais, Yoach, additional, Gingold, Hila, additional, Peles, Shani, additional, Chomsky, Elad, additional, Viukov, Sergey, additional, Buenrostro, Jason D., additional, Scognamiglio, Roberta, additional, Weinberger, Leehee, additional, Manor, Yair S., additional, Krupalnik, Vladislav, additional, Zerbib, Mirie, additional, Hezroni, Hadas, additional, Jaitin, Diego Adhemar, additional, Larastiaso, David, additional, Gilad, Shlomit, additional, Benjamin, Sima, additional, Gafni, Ohad, additional, Mousa, Awni, additional, Ayyash, Muneef, additional, Sheban, Daoud, additional, Bayerl, Jonathan, additional, Aguilera-Castrejon, Alejandro, additional, Massarwa, Rada, additional, Maza, Itay, additional, Hanna, Suhair, additional, Stelzer, Yonatan, additional, Ulitsky, Igor, additional, Greenleaf, William J., additional, Tanay, Amos, additional, Trumpp, Andreas, additional, Amit, Ido, additional, Pilpel, Yitzhak, additional, Novershtern, Noa, additional, and Hanna, Jacob H., additional

Published
2018
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