Article
Multidisciplinary Sciences
Camille Boudreau-Pinsonneault, Luke Ajay David, Jose Alex Lourenco Fernandes Fernandes, Awais Javed, Michel Fries, Pierre Mattar, Michel Cayouette
Summary: This study demonstrates that coexpression of early temporal identity transcription factors Ikzf1 and Ikzf4 can directly convert mouse retinal glial cells into photoreceptor cells and reprogram mouse embryonic fibroblasts into neurons. These findings uncover the potential of temporal identity factors in reprogramming terminally differentiated cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Genetics & Heredity
Han Jiang, Guoxin Li
Summary: Transcription factors play a crucial role in regulating epigenetic reprogramming in different cancer types, thereby altering the molecular and clinical phenotypes of cancer.
FRONTIERS IN GENETICS
(2023)
Article
Biology
Amrita A. Iyer, Ishwar Hosamani, John D. Nguyen, Tiantian Cai, Sunita Singh, Melissa M. McGovern, Lisa Beyer, Hongyuan Zhang, Hsin- Jen, Rizwan Yousaf, Onur Birol, Jenny J. Sun, Russell S. Ray, Yehoash Raphael, Neil Segil, Andrew K. Groves, Brian S. Kim
Summary: Reprogramming of the cochlea with hair-cell-specific transcription factors such as ATOH1 has been proposed for treating hearing loss. However, the efficiency of hair cell reprogramming declines as the cochlea matures. A combination of ATOH1, GFI1, and POU4F3 can reprogram non-sensory cells of the cochlea to a hair cell fate, but the resulting cells are less mature compared to those generated at an earlier stage. Epigenetic accessibility and signaling from hair cells to supporting cells, including Notch signaling, are key factors that impede hair cell reprogramming in older animals.
Article
Microbiology
Tomoki Inagaki, Kang-Hsin Wang, Ashish Kumar, Chie Izumiya, Hiroki Miura, Somayeh Komaki, Ryan R. Davis, Clifford G. Tepper, Harutaka Katano, Michiko Shimoda, Yoshihiro Izumiya
Summary: KICS is a chronic inflammatory disease caused by KSHV infection, characterized by high KSHV viral load and sustained elevation of IL-6 levels. Prolonged exposure to vIL-6 leads to changes in chromatin landscape, resulting in increased cytokine production and higher risk of inflammatory response.
Article
Oncology
Ana P. Kutschat, Feda H. Hamdan, Xin Wang, Alexander Q. Wixom, Zeynab Najafova, Christine S. Gibhardt, Waltraut Kopp, Jochen Gaedcke, Philipp Strobel, Volker Ellenrieder, Ivan Bogeski, Elisabeth Hessmann, Steven A. Johnsen
Summary: Gemcitabine-resistant PDAC tumors show coamplification of RRM1 and STIM1, where RRM1 is required for resistance while high STIM1 levels lead to increased cytosolic calcium levels. This calcium influx impairs ER stress response and activates NFAT signaling, revealing a potential target for therapy in PDAC.
Editorial Material
Cell & Tissue Engineering
Pradeep Reddy, Sebastian Memczak, Juan Carlos Izpisua Belmonte
Summary: The study demonstrates that epigenetic reprogramming of RGCs by overexpressing Oct4, Sox2, and Klf4 can lead to axon regeneration and restoration of vision in a glaucoma model and aged mice.
Review
Microbiology
Mohamed-Ali Hakimi
Summary: Like many intracellular pathogens, Toxoplasma gondii uses effector proteins to manipulate host cells and promote transmission and persistence. This review summarizes how T. gondii effectors control the fate of infected cells and the outcome of infection through specific mechanisms.
ANNUAL REVIEW OF MICROBIOLOGY
(2022)
Article
Biochemical Research Methods
Jennifer Hammelman, Tulsi Patel, Michael Closser, Hynek Wichterle, David Gifford
Summary: This study compares nine computational methods for identifying reprogramming factors for cell differentiation. The researchers found that methods using chromatin accessibility performed the best, with an average identification rate of 50-60% of reprogramming factors in the top ten candidates. Among the chromatin accessibility methods, DeepAccess and diffTF showed the highest correlation with the ranked significance of transcription factor candidates. AME and diffTF were identified as optimal methods for transcription factor recovery, allowing for systematic prioritization of candidates in the design of new reprogramming protocols.
Review
Oncology
Amitava Basu, Vijay K. Tiwari
Summary: Cellular reprogramming involves rewiring the underlying epigenome to convert one cell type into another, holding great promise for therapeutic use in repairing damaged tissues and organs but facing key challenges in application.
CLINICAL EPIGENETICS
(2021)
Article
Multidisciplinary Sciences
Xueqin Sun, Olaf Klingbeil, Bin Lu, Caizhi Wu, Carlos Ballon, Meng Ouyang, Xiaoli S. Wu, Ying Jin, Yon Hwangbo, Yu-Han Huang, Tim D. D. Somerville, Kenneth Chang, Jung Park, Taemoon Chung, Scott K. K. Lyons, Junwei Shi, Hannes Vogel, Michael Schulder, Christopher R. R. Vakoc, Alea A. A. Mills
Summary: Research uncovers a GBM-specific epigenetic mechanism where the chromatin regulator BRD8 inhibits p53 transactivation by maintaining H2AZ occupancy at p53 target loci, leading to sustained proliferation in TP53 wild-type GBM.
Article
Biology
Atrayee Bhattacharya, Atsushi Fushimi, Keyi Wang, Nami Yamashita, Yoshihiro Morimoto, Satoshi Ishikawa, Tatsuaki Daimon, Tao Liu, Song Liu, Mark D. Long, Donald Kufe
Summary: Chronic inflammation plays a crucial role in promoting cancer progression through epigenetic reprogramming. In this study, we demonstrate that the MUC1-C protein, activated by the NF-kappa B pathway, regulates H3K4 methylation levels and the expression of COMPASS SET1A/SETD1A and WDR5 genes. Furthermore, MUC1-C, along with other proteins, is involved in the expression of key regulators of pluripotency network and stemness.
COMMUNICATIONS BIOLOGY
(2023)
Article
Genetics & Heredity
Xiaodong Lu, Ka-wing Fong, Fang Wang, Galina Gritsina, Sylvan C. Baca, Jacob E. Berchuck, Jenny Ross, Eva Corey, Navdeep Chandel, William J. Catalona, Ximing Yang, Matthew L. Freedman, Jonathan C. Zhao, Jindan Yu, Lourdes T. Brea, Sandor Spisak, CoIm Morrissey
Summary: The study reveals that HOXB13 suppresses lipogenic transcriptional program in prostate cancer through HDAC3 recruitment, which inhibits tumor metastasis. Loss or mutation of HOXB13 leads to lipid accumulation in PCa cells, promoting cell motility and tumor metastasis. This study provides important insights into the roles of HOXB13 in prostate cancer progression and metastasis.
Article
Biology
Joao C. Sabino, Madalena R. de Almeida, Patricia L. Abreu, Ana M. Ferreira, Paulo Caldas, Marco M. Domingues, Nuno C. Santos, Claus M. Azzalin, Ana Rita Grosso, Sergio Fernandes de Almeida
Summary: The activity of TET enzymes promotes the formation of R-loops, revealing new mechanisms of gene expression regulation.
Review
Biochemistry & Molecular Biology
Deepika Puri, Wolfgang Wagner
Summary: Reprogramming towards pluripotency can rejuvenate cells, reversing age-associated molecular features and evading replicative senescence. However, complete reprogramming can lead to loss of cellular identity and risk of teratoma formation. Limited exposure to reprogramming factors can partially reset epigenetic ageing clocks while maintaining cellular identity. The relationship between rejuvenation and pluripotency, as well as alternative rejuvenation approaches, are discussed in this review.
Article
Biochemistry & Molecular Biology
Anindya Dutta, Nilanjana Maji, Pallabi Sengupta, Nilanjan Banerjee, Swarnali Kar, Gopeswar Mukherjee, Subhrangsu Chatterjee, Moitri Basu
Summary: Our study identified the crucial role of nucleolin in facilitating SP1 transcription factor binding to the ZEB1 promoter, leading to the activation of ZEB1 transcription. Stabilization of G-quadruplex with TMPyP4 represses ZEB1 transcription and inhibits cell invasiveness. These findings suggest that small molecule induced G-quadruplex stabilization may serve as a potential molecular switch to regulate gene expression.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Multidisciplinary Sciences
Carlos A. Aguilar, Anna Shcherbina, Darrell O. Ricke, Ramona Pop, Christopher T. Carrigan, Casey A. Gifford, Maria L. Urso, Melissa A. Kottke, Alexander Meissner
SCIENTIFIC REPORTS
(2015)
Editorial Material
Cell Biology
Casey A. Gifford, Deepak Srivastava
NATURE CELL BIOLOGY
(2016)
Article
Cell & Tissue Engineering
Carlos A. Aguilar, Ramona Pop, Anna Shcherbina, Alain Watts, Ronald W. Matheny, Davide Cacchiarelli, Woojin M. Han, Eunjung Shin, Shadi A. Nakhai, Young C. Jang, Christopher T. Carrigan, Casey A. Gifford, Melissa A. Kottke, Marcella Cesana, Jackson Lee, Maria L. Urso, Alexander Meissner
Article
Multidisciplinary Sciences
Jessica C. Butts, Dylan A. McCreedy, Jorge Alexis Martinez-Vargas, Frederico N. Mendoza-Camacho, Tracy A. Hookway, Casey A. Gifford, Praveen Taneja, Linda Noble-Haeusslein, Todd C. McDevitt
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Genetics & Heredity
Julie Donaghey, Sudhir Thakurela, Jocelyn Charlton, Jennifer S. Chen, Zachary D. Smith, Hongcang Gu, Ramona Pop, Kendell Clement, Elena K. Stamenova, Rahul Karnik, David R. Kelley, Casey A. Gifford, Davide Cacchiarelli, John L. Rinn, Andreas Gnirke, Michael J. Ziller, Alexander Meissner
Article
Cell & Tissue Engineering
Nicole R. Stone, Casey A. Gifford, Reuben Thomas, Karishma J. B. Pratt, Kaitlen Samse-Knapp, Tamer M. A. Mohamed, Ethan M. Radzinsky, Amelia Schricker, Lin Ye, Pengzhi Yu, Joke G. van Bemmel, Kathryn N. Ivey, Katherine S. Pollard, Deepak Srivastava
Article
Multidisciplinary Sciences
T. Yvanka de Soysa, Sanjeev S. Ranade, Satoshi Okawa, Srikanth Ravichandran, Yu Huang, Hazel T. Salunga, Amelia Schricker, Antonio del Sol, Casey A. Gifford, Deepak Srivastava
Article
Multidisciplinary Sciences
Casey A. Gifford, Sanjeev S. Ranade, Ryan Samarakoon, Hazel T. Salunga, T. Yvanka de Soysa, Yu Huang, Ping Zhou, Arye Elfenbein, Stacia K. Wyman, Yen Kim Bui, Kimberly R. Cordes Metzler, Philip Ursell, Kathryn N. Ivey, Deepak Srivastava
Article
Multidisciplinary Sciences
Christina Theodoris, Ping Zhou, Lei Liu, Yu Zhang, Tomohiro Nishino, Yu Huang, Aleksandra Kostina, Sanjeev S. Ranade, Casey A. Gifford, Vladimir Uspenskiy, Anna Malashicheva, Sheng Ding, Deepak Srivastava
Summary: By using a machine-learning approach, small molecules that can broadly correct dysregulated gene networks in a human heart disease model were identified, with the most efficacious candidate successfully preventing and treating AV disease in a mouse model.
Article
Multidisciplinary Sciences
Michael Alexanian, Pawel F. Przytycki, Rudi Micheletti, Arun Padmanabhan, Lin Ye, Joshua G. Travers, Barbara Gonzalez-Teran, Ana Catarina Silva, Qiming Duan, Sanjeev S. Ranade, Franco Felix, Ricardo Linares-Saldana, Li Li, Clara Youngna Lee, Nandhini Sadagopan, Angelo Pelonero, Yu Huang, Gaia Andreoletti, Rajan Jain, Timothy A. McKinsey, Michael G. Rosenfeld, Casey A. Gifford, Katherine S. Pollard, Saptarsi M. Haldar, Deepak Srivastava
Summary: In diseased organs, stress-activated signalling cascades alter chromatin, triggering maladaptive cell state transitions. Inhibition of BET proteins alleviates cardiac dysfunction and reveals a reversible transcriptional switch in fibroblasts. This study identifies MEOX1 as a central regulator of fibroblast activation associated with cardiac dysfunction, providing potential targets for treating fibrotic disease.
Article
Biochemistry & Molecular Biology
Barbara Gonzalez-Teran, Maureen Pittman, Franco Felix, Reuben Thomas, Desmond Richmond-Buccola, Ruth Huttenhain, Krishna Choudhary, Elisabetta Moroni, Mauro W. Costa, Yu Huang, Arun Padmanabhan, Michael Alexanian, Clara Youngna Lee, Bonnie E. J. Maven, Kaitlen Samse-Knapp, Sarah U. Morton, Michael McGregor, Casey A. Gifford, J. G. Seidman, Christine E. Seidman, Bruce D. Gelb, Giorgio Colombo, Bruce R. Conklin, Brian L. Black, Benoit G. Bruneau, Nevan J. Krogan, Katherine S. Pollard, Deepak Srivastava
Summary: This study identifies genetic variants associated with congenital heart disease (CHD) and prioritizes and screens these variants using protein interactome analysis, leading to the identification of potential causative genes for CHD.
Article
Genetics & Heredity
Nirmal Vadgama, Alexander Kreymerman, Jackie Campbell, Olga Shamardina, Christiane Brugger, Genomics England Research Consortium, Alexandra M. Deaconescu, Richard T. Lee, Christopher J. Penkett, Casey A. Gifford, Mark Mercola, Jamal Nasir, Ioannis Karakikes
Summary: COVID-19 susceptibility and progression are closely correlated with age, gender, ethnicity, and pre-existing health conditions. Host genetics, including variants in the ACE2 receptor, may play a role in determining COVID-19 risk and could partially account for differences in disease susceptibility among ethnic groups.
FRONTIERS IN GENETICS
(2022)
Article
Cardiac & Cardiovascular Systems
Lili Zhu, Krishna Choudhary, Barbara Gonzalez-Teran, Yen-Sin Ang, Reuben Thomas, Nicole R. Stone, Lei Liu, Ping Zhou, Chenchen Zhu, Hongmei Ruan, Yu Huang, Shibo Jin, Angelo Pelonero, Frances Koback, Arun Padmanabhan, Nandhini Sadagopan, Austin Hsu, Mauro W. Costa, Casey A. Gifford, Joke van Bemmel, Ruth Huttenhain, Vasanth Vedantham, Bruce R. Conklin, Brian L. Black, Benoit G. Bruneau, Lars Steinmetz, Nevan J. Krogan, Katherine S. Pollard, Deepak Srivastava
Summary: This study reveals that GATA4 regulates cell type-specific alternative splicing in human induced pluripotent stem cell-derived cardiac progenitors through direct interaction with RNA and the spliceosome.
Meeting Abstract
Hematology
Priscila Ferreira Slepicka, Kelsea M. Hubka, Hanh Dan Nguyen, Abdulvasey Mohammed, Jing Wang, Casey Gifford, Vittorio Sebastiano, Katja G. Weinacht
Article
Genetics & Heredity
Nirmal Vadgama, Mohamed Ameen, Laksshman Sundaram, Sadhana Gaddam, Casey Gifford, Jamal Nasir, Ioannis Karakikes
Summary: This study provides important insights into the genetic etiology of cardiomyopathies, highlighting the contribution of variants in noncoding regulatory regions and oligogenic inheritance mechanisms. The findings suggest that a combination of prioritized variants and genetic modifiers play a role in the development of cardiomyopathies. Additionally, rare noncoding variants in regulatory elements of known cardiomyopathy genes were found to be associated with the disease, uncovering potential targets for future investigations.
