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135 results on '"Reyes, Jaime M."'

1. Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging

Author

Liu, Ling, Kim, Soochi, Buckley, Matthew T, Reyes, Jaime M, Kang, Jengmin, Tian, Lei, Wang, Mingqiang, Lieu, Alexander, Mao, Michelle, Rodriguez-Mateo, Cristina, Ishak, Heather D, Jeong, Mira, Wu, Joseph C, Goodell, Margaret A, Brunet, Anne, and Rando, Thomas A

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Physical Activity, Stem Cell Research, Aging, Stem Cell Research - Nonembryonic - Human, Genetics, 1.1 Normal biological development and functioning, Inflammatory and immune system, Mice, Animals, Hematopoietic Stem Cells, Physical Conditioning, Animal, Transcriptome, Gene Expression Profiling, Muscle, Skeletal, Stem Cell Niche, Mammals, aging, exercise, hematopoietic stem cells, inflammation, muscle stem cells, myofibers, neural stem cells, scRNA-seq, skeletal muscle, subventricular zone, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Exercise has the ability to rejuvenate stem cells and improve tissue regeneration in aging animals. However, the cellular and molecular changes elicited by exercise have not been systematically studied across a broad range of cell types in stem cell compartments. We subjected young and old mice to aerobic exercise and generated a single-cell transcriptomic atlas of muscle, neural, and hematopoietic stem cells with their niche cells and progeny, complemented by whole transcriptome analysis of single myofibers. We found that exercise ameliorated the upregulation of a number of inflammatory pathways associated with old age and restored aspects of intercellular communication mediated by immune cells within these stem cell compartments. Exercise has a profound impact on the composition and transcriptomic landscape of circulating and tissue-resident immune cells. Our study provides a comprehensive view of the coordinated responses of multiple aged stem cells and niche cells to exercise at the transcriptomic level.

Published
2023

2. Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain

Author

Buckley, Matthew T, Sun, Eric D, George, Benson M, Liu, Ling, Schaum, Nicholas, Xu, Lucy, Reyes, Jaime M, Goodell, Margaret A, Weissman, Irving L, Wyss-Coray, Tony, Rando, Thomas A, and Brunet, Anne

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, Aging, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Mice, Animals, Rejuvenation, Cellular Senescence, Brain, Neurogenesis, Clinical sciences
Abstract

The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop 'aging clocks' based on single-cell transcriptomics to characterize cell-type-specific aging and rejuvenation. We generated single-cell transcriptomes from the subventricular zone neurogenic region of 28 mice, tiling ages from young to old. We trained single-cell-based regression models to predict chronological age and biological age (neural stem cell proliferation capacity). These aging clocks are generalizable to independent cohorts of mice, other regions of the brains, and other species. To determine if these aging clocks could quantify transcriptomic rejuvenation, we generated single-cell transcriptomic datasets of neurogenic regions for two interventions-heterochronic parabiosis and exercise. Aging clocks revealed that heterochronic parabiosis and exercise reverse transcriptomic aging in neurogenic regions, but in different ways. This study represents the first development of high-resolution aging clocks from single-cell transcriptomic data and demonstrates their application to quantify transcriptomic rejuvenation.

Published
2023

4. Hematologic DNMT3A reduction and high-fat diet synergize to promote weight gain and tissue inflammation

Author

Reyes, Jaime M., Tovy, Ayala, Zhang, Linda, Bortoletto, Angelina S., Rosas, Carina, Chen, Chun-Wei, Waldvogel, Sarah M., Guzman, Anna G., Aguilar, Rogelio, Gupta, Sinjini, Liu, Ling, Buckley, Matthew T., Patel, Kalyani R., Marcogliese, Andrea N., Li, Yumei, Curry, Choladda V., Rando, Thomas A., Brunet, Anne, Parchem, Ronald J., Rau, Rachel E., and Goodell, Margaret A.

Published
2024
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5. DNMT3A-coordinated splicing governs the stem state switch towards differentiation in embryonic and haematopoietic stem cells

Author

Ramabadran, Raghav, Wang, Jarey H., Reyes, Jaime M., Guzman, Anna G., Gupta, Sinjini, Rosas, Carina, Brunetti, Lorenzo, Gundry, Michael C., Tovy, Ayala, Long, Hali, Gu, Tianpeng, Cullen, Sean M., Tyagi, Siddhartha, Rux, Danielle, Kim, Jean J., Kornblau, Steven M., Kyba, Michael, Stossi, Fabio, Rau, Rachel E., Takahashi, Koichi, Westbrook, Thomas F., and Goodell, Margaret A.

Published
2023
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6. SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation

Author

Chen, Chun-Wei, Zhang, Linda, Dutta, Ravi, Niroula, Abhishek, Miller, Peter G., Gibson, Christopher J., Bick, Alexander G., Reyes, Jaime M., Lee, Yi-Tang, Tovy, Ayala, Gu, Tianpeng, Waldvogel, Sarah, Chen, Yi-Hung, Venters, Bryan J., Estève, Pierre-Olivier, Pradhan, Sriharsa, Keogh, Michael-Christopher, Natarajan, Pradeep, Takahashi, Koichi, Sperling, Adam S., and Goodell, Margaret A.

Published
2023
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8. Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice

Author

Sportoletti, Paolo, Sorcini, Daniele, Guzman, Anna G., Reyes, Jaime M., Stella, Arianna, Marra, Andrea, Sartori, Sara, Brunetti, Lorenzo, Rossi, Roberta, Papa, Beatrice Del, Adamo, Francesco Maria, Pianigiani, Giulia, Betti, Camilla, Scialdone, Annarita, Guarente, Valerio, Spinozzi, Giulio, Tini, Valentina, Martelli, Maria Paola, Goodell, Margaret A., and Falini, Brunangelo

Published
2021
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9. SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation

Author

Chen, Chun-Wei, primary, Zhang, Linda, additional, Dutta, Ravi, additional, Niroula, Abhishek, additional, Miller, Peter G., additional, Gibson, Christopher J., additional, Bick, Alexander G., additional, Reyes, Jaime M., additional, Lee, Yi-Tang, additional, Tovy, Ayala, additional, Gu, Tianpeng, additional, Waldvogel, Sarah, additional, Chen, Yi-Hung, additional, Venters, Bryan J., additional, Estève, Pierre-Olivier, additional, Pradhan, Sriharsa, additional, Keogh, Michael-Christopher, additional, Natarajan, Pradeep, additional, Takahashi, Koichi, additional, Sperling, Adam S., additional, and Goodell, Margaret A., additional

Published
2024
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11. BET bromodomain proteins regulate enhancer function during adipogenesis

Author

Brown, Jonathan D., Feldman, Zachary B., Doherty, Sean P., Reyes, Jaime M., Rahl, Peter B., Lin, Charles Y., Sheng, Quanhu, Duan, Qiong, Federation, Alexander J., Kung, Andrew L., Haldar, Saptarsi M., Young, Richard A., Plutzky, Jorge, and Bradner, James E.

Published
2018

12. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment

Author

Winter, Georg E., Mayer, Andreas, Buckley, Dennis L., Erb, Michael A., Roderick, Justine E., Vittori, Sarah, Reyes, Jaime M., di Iulio, Julia, Souza, Amanda, Ott, Christopher J., Roberts, Justin M., Zeid, Rhamy, Scott, Thomas G., Paulk, Joshiawa, Lachance, Kate, Olson, Calla M., Dastjerdi, Shiva, Bauer, Sophie, Lin, Charles Y., Gray, Nathanael S., Kelliher, Michelle A., Churchman, L. Stirling, and Bradner, James E.

Published
2017
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15. Data from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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16. Supplementary Figures S1 - S5, Tables S1 - S2 from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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17. Supplementary Table 3 from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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18. Data from Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor

Author

Huang, Yung-Hsin, primary, Chen, Chun-Wei, primary, Sundaramurthy, Venkatasubramaniam, primary, Słabicki, Mikołaj, primary, Hao, Dapeng, primary, Watson, Caroline J., primary, Tovy, Ayala, primary, Reyes, Jaime M., primary, Dakhova, Olga, primary, Crovetti, Brielle R., primary, Galonska, Christina, primary, Lee, Minjung, primary, Brunetti, Lorenzo, primary, Zhou, Yubin, primary, Tatton-Brown, Katrina, primary, Huang, Yun, primary, Cheng, Xiaodong, primary, Meissner, Alexander, primary, Valk, Peter J.M., primary, Van Maldergem, Lionel, primary, Sanders, Mathijs A., primary, Blundell, Jamie R., primary, Li, Wei, primary, Ebert, Benjamin L., primary, and Goodell, Margaret A., primary

Published
2023
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19. Supplementary Table from Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor

Author

Huang, Yung-Hsin, primary, Chen, Chun-Wei, primary, Sundaramurthy, Venkatasubramaniam, primary, Słabicki, Mikołaj, primary, Hao, Dapeng, primary, Watson, Caroline J., primary, Tovy, Ayala, primary, Reyes, Jaime M., primary, Dakhova, Olga, primary, Crovetti, Brielle R., primary, Galonska, Christina, primary, Lee, Minjung, primary, Brunetti, Lorenzo, primary, Zhou, Yubin, primary, Tatton-Brown, Katrina, primary, Huang, Yun, primary, Cheng, Xiaodong, primary, Meissner, Alexander, primary, Valk, Peter J.M., primary, Van Maldergem, Lionel, primary, Sanders, Mathijs A., primary, Blundell, Jamie R., primary, Li, Wei, primary, Ebert, Benjamin L., primary, and Goodell, Margaret A., primary

Published
2023
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20. Supplementary Figure from Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor

Author

Huang, Yung-Hsin, primary, Chen, Chun-Wei, primary, Sundaramurthy, Venkatasubramaniam, primary, Słabicki, Mikołaj, primary, Hao, Dapeng, primary, Watson, Caroline J., primary, Tovy, Ayala, primary, Reyes, Jaime M., primary, Dakhova, Olga, primary, Crovetti, Brielle R., primary, Galonska, Christina, primary, Lee, Minjung, primary, Brunetti, Lorenzo, primary, Zhou, Yubin, primary, Tatton-Brown, Katrina, primary, Huang, Yun, primary, Cheng, Xiaodong, primary, Meissner, Alexander, primary, Valk, Peter J.M., primary, Van Maldergem, Lionel, primary, Sanders, Mathijs A., primary, Blundell, Jamie R., primary, Li, Wei, primary, Ebert, Benjamin L., primary, and Goodell, Margaret A., primary

Published
2023
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21. Supplementary Methods from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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23. Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain

Author

Buckley, Matthew T., primary, Sun, Eric D., additional, George, Benson M., additional, Liu, Ling, additional, Schaum, Nicholas, additional, Xu, Lucy, additional, Reyes, Jaime M., additional, Goodell, Margaret A., additional, Weissman, Irving L., additional, Wyss-Coray, Tony, additional, Rando, Thomas A., additional, and Brunet, Anne, additional

Published
2022
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24. Clonal Competition: Cisplatin Treatment Drives Dominance of TP53- over Tet2-Mutant Stem Cell Clones

Author

Wohlan, Katharina, primary, Brunetti, Lorenzo, additional, Hsu, Joanne I., additional, Matatall, Katie A., additional, Murdaugh, Rebecca L., additional, Zhang, Linda, additional, Guzman, Anna, additional, Toups, Jack, additional, Hormaechea-Agulla, Daniel, additional, Rosas, Carina, additional, Kisiel, Meghan, additional, Kitano, Ayumi, additional, Hu, Tianyuan, additional, Tseng, Yu-Jung, additional, Kain, Bailee N., additional, Biesiadny, Sara, additional, Tiessen, Jonathan, additional, Li, Minhua, additional, Florez, Marcus, additional, Waldvogel, Sarah, additional, Kurtz, Kristen, additional, Jeong, Mira, additional, Le, Duy, additional, Morales-Mantilla, Daniel E., additional, Yan, Hannah, additional, Garcia Martell, Alejandra, additional, Kapadia, Chiraag D., additional, Huang, Yung-Hsin, additional, Conneely, Shannon E., additional, Aguilar, Rogelio, additional, Shi, Xiangguo, additional, Gu, Tianpeng, additional, Han, Hyojeong, additional, Jiang, Yajian, additional, Rogers, Jason, additional, Yonezawa, Taishi, additional, Thatavarty, Apoorva, additional, Cao, Ruoqiong, additional, Wathan, Trisha K., additional, Mercer, Nesa, additional, Kennedy, Daniel, additional, Tovy, Ayala, additional, Reyes, Jaime M., additional, Kimmel, Marek, additional, Huang, Yun, additional, Nakada, Daisuke, additional, King, Katherine Y., additional, and Goodell, Margaret A., additional

Published
2022
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25. Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor

Author

Huang, Yung Hsin, Chen, Chun Wei, Sundaramurthy, Venkatasubramaniam, Słabicki, Mikołaj, Hao, Dapeng, Watson, Caroline J., Tovy, Ayala, Reyes, Jaime M., Dakhova, Olga, Crovetti, Brielle R., Galonska, Christina, Lee, Minjung, Brunetti, Lorenzo, Zhou, Yubin, Brown, Katrina Tatton, Huang, Yun, Cheng, Xiaodong, Meissner, Alexander, Valk, Peter J.M., Van Maldergem, Lionel, Sanders, Mathijs A., Blundell, Jamie R., Li, Wei, Ebert, Benjamin L., Goodell, Margaret A., Huang, Yung Hsin, Chen, Chun Wei, Sundaramurthy, Venkatasubramaniam, Słabicki, Mikołaj, Hao, Dapeng, Watson, Caroline J., Tovy, Ayala, Reyes, Jaime M., Dakhova, Olga, Crovetti, Brielle R., Galonska, Christina, Lee, Minjung, Brunetti, Lorenzo, Zhou, Yubin, Brown, Katrina Tatton, Huang, Yun, Cheng, Xiaodong, Meissner, Alexander, Valk, Peter J.M., Van Maldergem, Lionel, Sanders, Mathijs A., Blundell, Jamie R., Li, Wei, Ebert, Benjamin L., and Goodell, Margaret A.

Abstract

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute myeloid leukemia development. We investigated the mechanisms underlying the instability using a CRISPR screen and uncovered regulated destruction of DNMT3A mediated by the DCAF8 E3 ubiquitin ligase adaptor. We establish a new paradigm to classify novel variants that has prognostic and potential therapeutic significance for patients with hematologic disease. SIGNIFICANCE: DNMT3A has emerged as the most important epigenetic regulator and tumor suppressor in the hematopoietic system. Our study represents a systematic and high-throughput method to characterize the molecular impact of DNMT3A missense mutations and the discovery of a regulated destruction mechanism of DNMT3A offering new prognostic and future therapeutic avenues.

Published
2022

26. Constitutive loss of DNMT3A causes morbid obesity through misregulation of adipogenesis

Author

Tovy, Ayala, primary, Reyes, Jaime M, additional, Zhang, Linda, additional, Huang, Yung-Hsin, additional, Rosas, Carina, additional, Daquinag, Alexes C, additional, Guzman, Anna, additional, Ramabadran, Raghav, additional, Chen, Chun-Wei, additional, Gu, Tianpeng, additional, Gupta, Sinjini, additional, Ortinau, Laura, additional, Park, Dongsu, additional, Cox, Aaron R, additional, Rau, Rachel E, additional, Hartig, Sean M, additional, Kolonin, Mikhail G, additional, and Goodell, Margaret A, additional

Published
2022
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27. Author response: Constitutive loss of DNMT3A causes morbid obesity through misregulation of adipogenesis

Author

Tovy, Ayala, primary, Reyes, Jaime M, additional, Zhang, Linda, additional, Huang, Yung-Hsin, additional, Rosas, Carina, additional, Daquinag, Alexes C, additional, Guzman, Anna, additional, Ramabadran, Raghav, additional, Chen, Chun-Wei, additional, Gu, Tianpeng, additional, Gupta, Sinjini, additional, Ortinau, Laura, additional, Park, Dongsu, additional, Cox, Aaron R, additional, Rau, Rachel E, additional, Hartig, Sean M, additional, Kolonin, Mikhail G, additional, and Goodell, Margaret A, additional

Published
2022
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28. Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging

Author

Liu, Ling, primary, Kim, Soochi, additional, Buckley, Matthew T., additional, Reyes, Jaime M., additional, Kang, Jengmin, additional, Tian, Lei, additional, Wang, Mingqiang, additional, Lieu, Alexander, additional, Mao, Michelle, additional, Rodriguez-Mateo, Cristina, additional, Ishak, Heather, additional, Jeong, Mira, additional, Wu, Joseph C., additional, Goodell, Margaret A., additional, Brunet, Anne, additional, and Rando, Thomas A., additional

Published
2022
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29. Cell type-specific aging clocks to quantify aging and rejuvenation in regenerative regions of the brain

Author

Buckley, Matthew T., primary, Sun, Eric, additional, George, Benson M., additional, Liu, Ling, additional, Schaum, Nicholas, additional, Xu, Lucy, additional, Reyes, Jaime M., additional, Goodell, Margaret A., additional, Weissman, Irving L., additional, Wyss-Coray, Tony, additional, Rando, Thomas A., additional, and Brunet, Anne, additional

Published
2022
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30. SRCAPmutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation

Author

Chen, Chun-Wei, Zhang, Linda, Dutta, Ravi, Niroula, Abhishek, Miller, Peter G., Gibson, Christopher J., Bick, Alexander G., Reyes, Jaime M., Lee, Yi-Tang, Tovy, Ayala, Gu, Tianpeng, Waldvogel, Sarah, Chen, Yi-Hung, Venters, Bryan J., Estève, Pierre-Olivier, Pradhan, Sriharsa, Keogh, Michael-Christopher, Natarajan, Pradeep, Takahashi, Koichi, Sperling, Adam S., and Goodell, Margaret A.

Published
2024
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31. Tissue-Biased Expansion of DNMT3A-Mutant Clones in a Mosaic Individual Is Associated with Conserved Epigenetic Erosion

Author

Tovy, Ayala, Reyes, Jaime M., Gundry, Michael C., Brunetti, Lorenzo, Lee-Six, Henry, Petljak, Mia, Park, Hyun Jung, Guzman, Anna G., Rosas, Carina, Jeffries, Aaron R., Baple, Emma, Mill, Jonathan, Crosby, Andrew H., Sency, Valerie, Xin, Baozhong, Machado, Heather E., Castillo, Danielle, Weitzel, Jeffrey N., Li, Wei, Stratton, Michael R., Campbell, Peter J., Wang, Heng, Sanders, Mathijs A., and Goodell, Margaret A.

Published
2020
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32. Constitutive loss of DNMT3A causes morbid obesity through misregulation of adipogenesis

Author

Tovy, Ayala, primary, Reyes, Jaime M., additional, Zhang, Linda, additional, Huang, Yung-Hsin, additional, Rosas, Carina, additional, Daquinag, Alexes C., additional, Guzman, Anna G., additional, Ramabadran, Raghav, additional, Chen, Chun-Wei, additional, Gu, Tianpeng, additional, Gupta, Sinjini, additional, Ortinau, Laura, additional, Park, Dongsu, additional, Cox, Aaron R., additional, Rau, Rachel E, additional, Hartig, Sean M., additional, Kolonin, Mikhail G, additional, and Goodell, Margaret A., additional

Published
2021
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33. Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor

Author

Huang, Yung-Hsin, primary, Chen, Chun-Wei, additional, Sundaramurthy, Venkatasubramaniam, additional, Słabicki, Mikołaj, additional, Hao, Dapeng, additional, Watson, Caroline J., additional, Tovy, Ayala, additional, Reyes, Jaime M., additional, Dakhova, Olga, additional, Crovetti, Brielle R., additional, Galonska, Christina, additional, Lee, Minjung, additional, Brunetti, Lorenzo, additional, Zhou, Yubin, additional, Tatton-Brown, Katrina, additional, Huang, Yun, additional, Cheng, Xiaodong, additional, Meissner, Alexander, additional, Valk, Peter J.M., additional, Van Maldergem, Lionel, additional, Sanders, Mathijs A., additional, Blundell, Jamie R., additional, Li, Wei, additional, Ebert, Benjamin L., additional, and Goodell, Margaret A., additional

Published
2021
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34. Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome

Author

Tovy, Ayala, primary, Rosas, Carina, additional, Gaikwad, Amos S., additional, Medrano, Geraldo, additional, Zhang, Linda, additional, Reyes, Jaime M., additional, Huang, Yung-Hsin, additional, Arakawa, Tastuhiko, additional, Kurtz, Kristen, additional, Conneely, Shannon E., additional, Guzman, Anna G., additional, Aguilar, Rogelio, additional, Gao, Anne, additional, Chen, Chun-Wei, additional, Kim, Jean J., additional, Carter, Melissa T., additional, Lasa-Aranzasti, Amaia, additional, Valenzuela, Irene, additional, Van Maldergem, Lionel, additional, Brunetti, Lorenzo, additional, Hicks, M. John, additional, Marcogliese, Andrea N., additional, Goodell, Margaret A., additional, and Rau, Rachel E., additional

Published
2021
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35. Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice

Author

Sportoletti, Paolo, primary, Sorcini, Daniele, additional, Guzman, Anna G., additional, Reyes, Jaime M., additional, Stella, Arianna, additional, Marra, Andrea, additional, Sartori, Sara, additional, Brunetti, Lorenzo, additional, Rossi, Roberta, additional, Papa, Beatrice Del, additional, Adamo, Francesco Maria, additional, Pianigiani, Giulia, additional, Betti, Camilla, additional, Scialdone, Annarita, additional, Guarente, Valerio, additional, Spinozzi, Giulio, additional, Tini, Valentina, additional, Martelli, Maria Paola, additional, Goodell, Margaret A., additional, and Falini, Brunangelo, additional

Published
2020
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36. Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities

Author

Rogers, Jason H., primary, Gupta, Rohit, additional, Reyes, Jaime M., additional, Gundry, Michael C., additional, Medrano, Geraldo, additional, Guzman, Anna, additional, Song, Tidie, additional, Johnson, Cade, additional, Barnes, Sean, additional, Cristobal, Carlo D. D., additional, Brunetti, Lorenzo, additional, Goodell, Margaret A., additional, and Rau, Rachel E., additional

Published
2020
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39. High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

Author

Labbé, David P., primary, Zadra, Giorgia, additional, Yang, Meng, additional, Reyes, Jaime M., additional, Lin, Charles Y., additional, Cacciatore, Stefano, additional, Ebot, Ericka M., additional, Creech, Amanda L., additional, Giunchi, Francesca, additional, Fiorentino, Michelangelo, additional, Elfandy, Habiba, additional, Syamala, Sudeepa, additional, Karoly, Edward D., additional, Alshalalfa, Mohammed, additional, Erho, Nicholas, additional, Ross, Ashley, additional, Schaeffer, Edward M., additional, Gibb, Ewan A., additional, Takhar, Mandeep, additional, Den, Robert B., additional, Lehrer, Jonathan, additional, Karnes, R. Jeffrey, additional, Freedland, Stephen J., additional, Davicioni, Elai, additional, Spratt, Daniel E., additional, Ellis, Leigh, additional, Jaffe, Jacob D., additional, DʼAmico, Anthony V., additional, Kantoff, Philip W., additional, Bradner, James E., additional, Mucci, Lorelei A., additional, Chavarro, Jorge E., additional, Loda, Massimo, additional, and Brown, Myles, additional

Published
2019
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40. Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Kimmerling, Robert John, Manalis, Scott R, Mowery, Cody T., Reyes, Jaime M., Cabal-Hierro, Lucia, Higby, Kelly J., Karlin, Kristen L., Wang, Jarey H., Cejas, Paloma, Lim, Klothilda, Li, Hubo, Furusawa, Takashi, Long, Henry W., Pellman, David, Chapuy, Bjoern, Bustin, Michael, Westbrook, Thomas F., Lin, Charles Y., Lane, Andrew A., Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Kimmerling, Robert John, Manalis, Scott R, Mowery, Cody T., Reyes, Jaime M., Cabal-Hierro, Lucia, Higby, Kelly J., Karlin, Kristen L., Wang, Jarey H., Cejas, Paloma, Lim, Klothilda, Li, Hubo, Furusawa, Takashi, Long, Henry W., Pellman, David, Chapuy, Bjoern, Bustin, Michael, Westbrook, Thomas F., Lin, Charles Y., and Lane, Andrew A.

Abstract

Down syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations with transcriptome changes, we performed paired exogenous spike-in normalized RNA and chromatin immunoprecipitation sequencing in DS models. Absolute normalization unmasks global amplification of gene expression associated with trisomy 21. Overexpression of the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulates transcriptional changes seen with triplication of a Down syndrome critical region on distal chromosome 21, and HMGN1 is necessary for B cell phenotypes in DS models. Absolute exogenous-normalized chromatin immunoprecipitation sequencing (ChIP-Rx) also reveals a global increase in histone H3K27 acetylation caused by HMGN1. Transcriptional amplification downstream of HMGN1 is enriched for stage-specific programs of B cells and B cell acute lymphoblastic leukemia, dependent on the developmental cellular context. These data offer a mechanistic explanation for DS transcriptional patterns and suggest that further study of HMGN1 and RNA amplification in diverse DS phenotypes is warranted. How trisomy 21 contributes to Down syndrome phenotypes, including increased leukemia risk, is not well understood. Mowery et al. use per-cell normalization approaches to reveal global transcriptional amplification in Down syndrome models. HMGN1 overexpression is sufficient to induce these alterations and promotes lineage-associated transcriptional programs, signaling, and B cell progenitor phenotypes.

Published
2019

41. Mosaic DNMT3A Germline Mutation As a Model for Mutant DNMT3A Competitive Advantage in the Blood Lineage

Author

Tovy, Ayala, primary, Park, Hyun Jung, additional, Reyes, Jaime M., additional, Guzman, Anna, additional, Rau, Rachel E., additional, Jeffries, Aaron, additional, Jonnathan, Mill, additional, Baple, Emma, additional, Crosby, Andrew, additional, Petljak, Mia, additional, Lee-Six, Henry, additional, Wang, Heng, additional, Baozhong, Xin, additional, Sanders, Mathijs A., additional, Campbell, Peter J., additional, Stratton, Michael, additional, Li, Wei, additional, and Goodell, Margaret, additional

Published
2018
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42. Precise Modeling of IKZF1 Alterations in Human B-Cell Acute Lymphoblastic Leukemia Cell Lines Reveals Distinct Chemosensitivity, Homing, and Engraftment Properties

Author

Rogers, Jason H., primary, Gupta, Rohit, additional, Reyes, Jaime M., additional, Brunetti, Lorenzo, additional, Gundry, Michael C., additional, Song, Tidie, additional, Johnson, Cade, additional, Cristobal, Carlo D. D., additional, Goodell, Margaret A., additional, and Rau, Rachel E., additional

Published
2018
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43. Large DNA Methylation Canyons Anchor Chromatin Loops Maintaining Hematopoietic Stem Cell Identity

Author

Jeong, Mira, primary, Huang, Xiangfan, additional, Zhang, Xiaotian, additional, Su, Jianzhong, additional, Shamim, Muhammad S, additional, Bochkov, Ivan D, additional, Reyes, Jaime M., additional, Jung, Haiyoung, additional, Heikamp, Emily Beth, additional, Aiden, Aviva P, additional, Li, Wei, additional, Aiden, Erez Lieberman, additional, and Goodell, Margaret A., additional

Published
2018
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44. BET bromodomain proteins regulate enhancer function during adipogenesis

Author

Massachusetts Institute of Technology. Department of Biology, Young, Richard A, Brown, Jonathan D., Feldman, Zachary B., Doherty, Sean P., Reyes, Jaime M., Rahl, Peter B., Lin, Charles Y., Sheng, Quanhu, Duan, Qiong, Federation, Alexander J., Kung, Andrew L., Haldar, Saptarsi M., Plutzky, Jorge, Bradner, James E., Young, Richard A., Massachusetts Institute of Technology. Department of Biology, Young, Richard A, Brown, Jonathan D., Feldman, Zachary B., Doherty, Sean P., Reyes, Jaime M., Rahl, Peter B., Lin, Charles Y., Sheng, Quanhu, Duan, Qiong, Federation, Alexander J., Kung, Andrew L., Haldar, Saptarsi M., Plutzky, Jorge, Bradner, James E., and Young, Richard A.

Published
2018

45. Bcordeficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3aloss in acute erythroid leukemia onset in mice

Author

Sportoletti, Paolo, Sorcini, Daniele, Guzman, Anna G., Reyes, Jaime M., Stella, Arianna, Marra, Andrea, Sartori, Sara, Brunetti, Lorenzo, Rossi, Roberta, Papa, Beatrice Del, Adamo, Francesco Maria, Pianigiani, Giulia, Betti, Camilla, Scialdone, Annarita, Guarente, Valerio, Spinozzi, Giulio, Tini, Valentina, Martelli, Maria Paola, Goodell, Margaret A., and Falini, Brunangelo

Abstract

Recurrent loss-of-function mutations of BCL6 co-repressor(BCOR)gene are found in about 4% of AML patients with normal karyotype and are associated with DNMT3amutations and poor prognosis. Therefore, new anti-leukemia treatments and mouse models are needed for this combinatorial AML genotype. For this purpose, we first generated a Bcor−/−knockout mouse model characterized by impaired erythroid development (macrocytosis and anemia) and enhanced thrombopoiesis, which are both features of myelodysplasia/myeloproliferative neoplasms. We then created and characterized double Bcor−/−/Dnmt3a−/−knockout mice. Interestingly, these animals developed a fully penetrant acute erythroid leukemia (AEL) characterized by leukocytosis secondary to the expansion of blasts expressing c-Kit+ and the erythroid marker Ter119, macrocytic anemia and progressive reduction of the thrombocytosis associated with loss of Bcoralone. Transcriptomic analysis of double knockout bone marrow progenitors revealed that aberrant erythroid skewing was induced by epigenetic changes affecting specific transcriptional factors (GATA1-2) and cell-cycle regulators (Mdm2, Tp53). These findings prompted us to investigate the efficacy of demethylating agents in AEL, with significant impact on progressive leukemic burden and mice overall survival. Information gained from our model expands the knowledge on the biology of AEL and may help designing new rational treatments for patients suffering from this high-risk leukemia.

Published
2021
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46. Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, additional, Reyes, Jaime M., additional, Li, Lewyn, additional, Rao, Prakash K., additional, Li, Fugen, additional, Lin, Charles Y., additional, Perry, Jennifer A., additional, Lawlor, Matthew A., additional, Federation, Alexander, additional, De Raedt, Thomas, additional, Li, Yvonne Y., additional, Liu, Yan, additional, Duarte, Melissa A., additional, Zhang, Yanxi, additional, Herter-Sprie, Grit S., additional, Kikuchi, Eiki, additional, Carretero, Julian, additional, Perou, Charles M., additional, Reibel, Jacob B., additional, Paulk, Joshiawa, additional, Bronson, Roderick T., additional, Watanabe, Hideo, additional, Brainson, Christine Fillmore, additional, Kim, Carla F., additional, Hammerman, Peter S., additional, Brown, Myles, additional, Cichowski, Karen, additional, Long, Henry, additional, Bradner, James E., additional, and Wong, Kwok-Kin, additional

Published
2016
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47. Abstract 2674: High fat diet accelerates MYC-driven prostate cancer through metabolic and epigenomic rewiring

Author

Labbe’, David P., primary, Zadra, Giorgia, additional, Yang, Meng, additional, Lin, Charles Y., additional, Reyes, Jaime M., additional, Cacciatore, Stefano, additional, Ebot, Ericka M., additional, Cotter, Maura B., additional, Creech, Amanda L., additional, Jaffe, Jacob D., additional, Kantoff, Philip W., additional, Bradner, James E., additional, Mucci, Lorelei A., additional, Chavarro, Jorge E., additional, Loda, Massimo, additional, and Brown, Myles, additional

Published
2016
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48. Loss of Dnmt3a Immortalizes Hematopoietic Stem Cells In Vivo.

Author

Mira Jeong, Hyun Jung Park, Celik, Hamza, Ostrander, Elizabeth L., Reyes, Jaime M., Guzman, Anna, Rodriguez, Benjamin, Yong Lei, Yeojin Lee, Lei Ding, Guryanova, Olga A., Wei Li, Goodell, Margaret A., and Challen, Grant A.

Abstract

Somatic mutations in DNMT3A are recurrent events across a range of blood cancers. Dnmt3a loss of function in hematopoietic stem cells (HSCs) skews divisions toward self-renewal at the expense of differentiation. Moreover, DNMT3A mutations can be detected in the blood of aging individuals, indicating that mutant cells outcompete normal HSCs over time. It is important to understand how these mutations provide a competitive advantage to HSCs. Here we show that Dnmt3a-null HSCs can regenerate over at least 12 transplant generations in mice, far exceeding the lifespan of normal HSCs. Molecular characterization reveals that this in vivo immortalization is associated with gradual and focal losses of DNA methylation at key regulatory regions associated with self-renewal genes, producing a highly stereotypical HSC phenotype in which epigenetic features are further buttressed. These findings lend insight into the preponderance of DNMT3A mutations in clonal hematopoiesis and the persistence of mutant clones after chemotherapy. [ABSTRACT FROM AUTHOR]

Published
2018
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49. Abstract A10: High-fat diet enhances MYC-driven prostate cancer through epigenomic and metabolomic rewiring

Author

Labbé, David P., primary, Zadra, Giorgia, additional, Ebot, Ericka M., additional, Lin, Charles Y., additional, Reyes, Jaime M., additional, Cacciatore, Stefano, additional, Cotter, Maura, additional, Creech, Amanda L., additional, Jaffe, Jacob D., additional, Kantoff, Philip W., additional, Bradner, James E., additional, Mucci, Lorelei A., additional, Loda, Massimo, additional, and Brown, Myles, additional

Published
2016
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50. SRCAPmutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation

Author

Chen, Chun-Wei, Zhang, Linda, Dutta, Ravi, Niroula, Abhishek, Miller, Peter G., Gibson, Christopher J., Bick, Alexander G., Reyes, Jaime M., Lee, Yi-Tang, Tovy, Ayala, Gu, Tianpeng, Waldvogel, Sarah, Chen, Yi-Hung, Venters, Bryan J., Estève, Pierre-Olivier, Pradhan, Sriharsa, Keogh, Michael-Christopher, Natarajan, Pradeep, Takahashi, Koichi, Sperling, Adam S., and Goodell, Margaret A.

Abstract

Somatic mutations accumulate in all cells with age and can confer a selective advantage, leading to clonal expansion over time. In hematopoietic cells, mutations in a subset of genes regulating DNA repair or epigenetics frequently lead to clonal hematopoiesis (CH). Here, we describe the context and mechanisms that lead to enrichment of hematopoietic stem cells (HSCs) with mutations in SRCAP, which encodes a chromatin remodeler that also influences DNA repair. We show that SRCAPmutations confer a selective advantage in human cells and in mice upon treatment with the anthracycline-class chemotherapeutic doxorubicin and bone marrow transplantation. Furthermore, Srcapmutations lead to a lymphoid-biased expansion, driven by loss of SRCAP-regulated H2A.Z deposition and increased DNA repair. Altogether, we demonstrate that SRCAP operates at the intersection of multiple pathways in stem and progenitor cells, offering a new perspective on the functional impact of genetic variants that promote stem cell competition in the hematopoietic system.

Published
2023
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