Review
Cell Biology
Tasnim H. Beacon, James R. Davie
Summary: The chicken erythrocyte model system is valuable for studying chromatin structure and function, with unique features allowing the separation of transcriptionally active chromatin and silenced chromatin. Recent studies have mapped transcriptionally active chromosomal domains in the chicken erythrocyte genome and reported detailed landscapes of histone modifications in relation to chromatin structural features.
Article
Biochemistry & Molecular Biology
V. Yu. Bairamukov, M. V. Filatov, R. A. Kovalev, N. D. Fedorova, R. A. Pantina, A. V. Ankudinov, E. G. Iashina, S. V. Grigoriev, E. Yu. Varfolomeeva
Summary: The resistance to deformation of nuclear chromatin is correlated with fundamental biological processes in the cell nucleus, such as transcription, as assessed by Atomic Force Microscopy (AFM).
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Cell Biology
Mingxuan Li, Yutao Shen, Yujia Xiong, Shuai Wang, Chuzhong Li, Jiwei Bai, Yazhuo Zhang
Summary: The study revealed that SMARCB1 functions as a tumor suppressor in chordoma by inhibiting the malignant phenotype of chordoma cells. SMARCB1 inhibits autophagy through direct binding to the ATG5 promoter, leading to decreased ATG5 expression and impaired autophagy. High ATG5 expression is associated with adverse outcomes in recurrent chordoma patients.
CELL PROLIFERATION
(2021)
Article
Biochemistry & Molecular Biology
Katja Lidschreiber, Lisa A. Jung, Henrik von der Emde, Kashyap Dave, Jussi Taipale, Patrick Cramer, Michael Lidschreiber
Summary: The study identified thousands of transcriptionally active enhancers in human cancer cells using transient transcriptome sequencing (TT-seq), which were associated with cell type-specific gene expression and enriched for genetic variants predisposing to cancer. Enhancer-promoter pairing analysis revealed around 40,000 putative E-P pairs enriched for transcription factors and cancer-associated genes. The cell type specificity and transcription activity of target genes increased with the number of paired putative enhancers, providing a rich resource for future gene regulation studies.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Article
Oncology
Zhi-Cheng He, Qing Liu, Kai-Di Yang, Cong Chen, Xiao-Ning Zhang, Wen-Ying Wang, Hui Zeng, Bin Wang, Yu-Qi Liu, Min Luo, Lei Li, Qin Niu, Hui-Min Lu, Tao Luo, Xiao-Hong Yao, Hai-Tao Guo, Jia-Le Ji, Mian-Fu Cao, Yu Shi, Yi-Fang Ping, Xiu-Wu Bian
Summary: This study revealed the gene amplification and protein overexpression of HOXA5 in glioma stem cells (GSCs) and its function in regulating GSC maintenance and downstream transcriptional effector. HOXA5 amplification serves as a genetic biomarker for predicting worse glioblastoma (GBM) outcome by enhancing PTPRZ1-mediated GSC survival.
Article
Multidisciplinary Sciences
Ana Nikolic, Francesca Maule, Anna Bobyn, Katrina Ellestad, Seungil Paik, Sajid A. Marhon, Parinaz Mehdipour, Xueqing Lun, Huey-Miin Chen, Claire Mallard, Alexander J. Hay, Michael J. Johnston, Christopher J. Gafuik, Franz J. Zemp, Yaoqing Shen, Nicoletta Ninkovic, Katalin Osz, Elodie Labit, N. Daniel Berger, Duncan K. Brownsey, John J. Kelly, Jeff Biernaskie, Peter B. Dirks, Darren J. Derksen, Steven J. M. Jones, Donna L. Senger, Jennifer A. Chan, Douglas J. Mahoney, Daniel D. De Carvalho, Marco Gallo
Summary: The histone variant macroH2A2 controls an epigenetic mechanism of self-renewal and suggests new treatment approaches for glioblastoma patients.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Huey-Miin Chen, Ana Nikolic, Divya Singhal, Marco Gallo
Summary: This review explores the relationship between cancer stem cells (CSCs) and treatment resistance in glioblastoma (GBM), as well as the intrinsic and extrinsic factors that contribute to epigenomic heterogeneity and therapy resistance. Understanding these mechanisms can provide promising applications for epigenetic treatment approaches in treating GBM.
Article
Immunology
Kota Itahashi, Takuma Irie, Junichiro Yuda, Shogo Kumagai, Tokiyoshi Tanegashima, Yi-Tzu Lin, Sho Watanabe, Yasushi Goto, Jun Suzuki, Keiju Aokage, Masahiro Tsuboi, Yosuke Minami, Genichiro Ishii, Yuichiro Ohe, Wataru Ise, Tomohiro Kurosaki, Yutaka Suzuki, Shohei Koyama, Hiroyoshi Nishikawa
Summary: Research has shown that Treg cells in the TME undergo a distinct open chromatin profile, with key transcription factors including BATF, IRF4, NF-κB, and NR4A, among which BATF serves as a crucial regulator influencing the differentiation and activation of Treg cells in the TME through epigenetic control of activation-associated gene expression. BATF deficiency may inhibit tumor growth, and high levels of BATF expression are associated with poor prognosis.
SCIENCE IMMUNOLOGY
(2022)
Article
Reproductive Biology
Matej Murin, Lucie Nemcova, Alexandra Bartkova, Ahmed Gad, Andrea Lucas-Hahn, Frantisek Strejcek, Radek Prochazka, Jozef Laurincik
Summary: The previous strong support for the statement that fully-grown porcine oocytes are transcriptionally quiescent is now challenged. A new study reveals differences in the transcription profiles between germinal vesicle (GV) and metaphase II (MII) oocytes. The study compares the transcription profiles of oocytes at different stages and identifies differentially transcribed mRNAs that are important for key processes during in vitro maturation.
Editorial Material
Biochemistry & Molecular Biology
Jack A. Collora, Ya-Chi Ho
Summary: The shock-and-kill strategy aims to reactivate HIV-1 latent reservoirs to enable immune clearance. A study by Einkauf et al. discovered that some persisting and proliferating HIV-1-infected cells have actively transcribing HIV-1 in permissive chromatin. However, silent proviruses in repressive chromatin are resistant to reactivation. Understanding the interactions between HIV-1 and chromatin, as well as the survival mechanisms of transcriptionally active HIV-1-infected cells, is of crucial importance.
Article
Cell & Tissue Engineering
Jiayi Chen, Guangqin Liu, Xinzheng Wang, Hao Hong, Tingting Li, Lin Li, Hongxiang Wang, Jiong Xie, Bohan Li, Ting Li, Dingyi Lu, Yakun Zhang, Haixin Zhao, Chengcheng Yao, Kaiqing Wen, Teng Li, Jing Chen, Shengming Wu, Kun He, Wei-Na Zhang, Jie Zhao, Na Wang, Qiuying Han, Qing Xia, Ji Qi, Juxiang Chen, Tao Zhou, Jianghong Man, Xue-Min Zhang, Ai-Ling Li, Xin Pan
Summary: This study explores the communication between glioblastoma stem cells (GSCs) and the microenvironment, revealing that GSCs secrete histamine to shape a pro-angiogenic tumor microenvironment. The secretion of histamine by GSCs is associated with the expression and modification of the HDC gene, and the histamine activates endothelial cells through the H1R-Ca2+-NF-kB axis, promoting angiogenesis and GBM progression. The findings suggest that targeting histamine could be a potential strategy for GBM therapy.
Article
Biology
Anne Helness, Jennifer Fraszczak, Charles Joly-Beauparlant, Halil Bagci, Christian Trahan, Kaifee Arman, Peiman Shooshtarizadeh, Riyan Chen, Marina Ayoub, Jean-Francois Cote, Marlene Oeffinger, Arnaud Droit, Tarik Moroy
Summary: The GFI1/CHD4 complexes play a critical role in regulating chromatin accessibility and histone modifications, thereby affecting the expression of target genes involved in various cellular processes in neutrophils. The interaction between GFI1 and CHD4 in granulo-monocytic precursors is essential for recruiting the NuRD complex to regulate gene expression, indicating the importance of chromatin remodeling complexes in myeloid differentiation.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Vittoria Guarda, Lea Schroeder, Michael Pawlita, Kristian Ikenberg, Niels J. Rupp, Wolfram Jochum, Sandro J. Stoeckli, Dana Holzinger, Martina A. Broglie
Summary: This study found that HPV infection can be detected in normal oropharyngeal tissue, but without transcriptional activity. This suggests that a multifocal virus-induced cancerization may not be associated with HPV-related OPSCC.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Aleksandra Kopacz, Damian Kloska, Jakub Fichna, Dominika Klimczyk, Magdalena Kopec, Alicja Jozkowicz, Aleksandra Piechota-Polanczyk
Summary: This study aimed to investigate the gender-dependent impact of NRF2 transcriptional deficiency on colon function and its relationship with inflammatory bowel disease (IBD). It was found that NRF2 transcriptional abrogation, similar to IL-10 deficiency, triggers functional and microscopic phenotypes resembling IBD, with females being more affected. The impaired distal colon motility is dependent on ER beta signaling, and targeting estrogen signaling seems to be a promising therapeutic strategy for colonic dysfunction.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
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
Oncology
Leihao Ren, Lingyang Hua, Zhongyuan Bao, Jiaojiao Deng, Daijun Wang, Jiawei Chen, Hong Chen, Tareq A. Juratli, Hiroaki Wakimoto, Ye Gong
Summary: This study evaluated the clinicopathological characteristics, radiology, and long-term outcomes of microcystic meningiomas (MM) and compared it with other subtypes of meningiomas. The results showed that the progression-free survival of MM was worse than other WHO grade 1 subtypes, but better than atypical meningiomas. Skull base location and higher Ki-67 index were identified as independent negative prognostic factors in MM.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Article
Oncology
Kazuhide Shimizu, Kaoru Tamura, Shoko Hara, Motoki Inaji, Yoji Tanaka, Daisuke Kobayashi, Takashi Sugawara, Hiroaki Wakimoto, Tadashi Nariai, Kenji Ishii, Ichiro Sakuma, Taketoshi Maehara
Summary: This study aimed to investigate the correlation between preoperative MET-PET signals and intraoperative 5-ALA-induced fluorescence in malignant brain tumor surgery. The results showed that strong tumor fluorescence correlated with high MET-PET uptake and cellular proliferation, providing valuable tumor biology information for surgery in situations where MET-PET is not accessible.
Article
Cell Biology
Shuo Wang, Yosuke Tanaka, Ying Xu, Sen Takeda, Nobutaka Hirokawa
Summary: This study proposes a diffusion-and-trapping hypothesis to explain the mechanism of Sonic hedgehog (Shh) gradient formation. The research found that in KIF3B-deficient mice, the Shh gradient was disrupted, leading to abnormal limb bud development. This phenotype was reproduced by transplanting FGF8b-soaked beads. The study also found that high and low PI3K signaling strengths determined the localization of Shh particles.
DEVELOPMENTAL CELL
(2022)
Article
Oncology
Lingyang Hua, Leihao Ren, Qian Wu, Jiaojiao Deng, Jiawei Chen, Haixia Cheng, Daijun Wang, Hong Chen, Qing Xie, Hiroaki Wakimoto, Ye Gong
Summary: This study aimed to investigate whether the loss of H3K27me3 could predict the risk of re-recurrence in recurrent meningiomas. The results showed that the loss of H3K27me3 expression was more common in recurrent meningiomas compared to primary meningiomas. Furthermore, the loss of H3K27me3 was associated with an earlier re-recurrence and predicted shorter progression-free survival in recurrent grade 1 and grade 2 meningiomas.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Correction
Multidisciplinary Sciences
Yang An, Baoshi Yuan, Pancheng Xie, Yue Gu, Zhiwei Liu, Tao Wang, Zhihao Li, Ying Xu, Yi Liu
NATURE COMMUNICATIONS
(2022)
Article
Biology
Justine Chee, Louise Lanoue, Dave L. Clary, Kendall Higgins, Lynette Bower, Ann Flenniken, Ruolin Guo, David Adams, Fatima Bosch, Robert E. Braun, Steve D. M. Brown, H. -J. Genie Chin, Mary Dickinson, Chih-Wei Hsu, Michael Dobbie, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason Heaney, Yann Herault, Martin Hrabe de Angelis, Fabio Mammano, Lauryl M. J. Nutter, Helen Parkinson, Chuan Qin, Toshi Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, Brian Brooks, Colin McKerlie, K. C. Kent Lloyd, Henrik Westerberg, Ala Moshiri
Summary: This study identified new genes and pathways associated with eye development through screening of mouse genes. These findings provide insights into the molecular and cellular mechanisms of eye development and could potentially contribute to the diagnosis and treatment of congenital blinding diseases.
Article
Biochemistry & Molecular Biology
Hui Zhang, Aifei Wang, Guangfei Li, Qiaocheng Zhai, Zhengyun Huang, Xiao Wang, Zihou Cao, Lulin Liu, Gongwen Liu, Bin Chen, Keyu Zhu, Ying Xu, Youjia Xu
Summary: Excessive iron accumulation is a risk factor for osteopenia and osteoporosis, and ferroptosis, a form of cell death, is related to iron-dependent lipid peroxide accumulation. This study reveals that ferroptosis is involved in excess-iron-induced bone loss and demonstrates elevated presence of the NOX4 enzyme in osteoporotic mice and humans. Mechanistically, iron induces dissociation of the iron regulatory protein 1 (IRP1) from the iron-response element-like (IRE-like) sequences in the NOX4 locus, leading to increased NOX4 transcription and lipid peroxide accumulation. Treatment with a ferroptosis inhibitor and an iron chelator shows potential for preventing osteoporotic bone loss.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Kok-Siong Chen, Clemens Reinshagen, Thijs A. Van Schaik, Filippo Rossignoli, Paulo Borges, Natalia Claire Mendonca, Reza Abdi, Brennan Simon, David A. Reardon, Hiroaki Wakimoto, Khalid Shah
Summary: We developed a bifunctional whole cancer cell-based therapeutic that can directly kill tumor cells and stimulate the immune system. By modifying tumor cells using CRISPR-Cas9 and engineering them to release immunomodulatory agents, these therapeutic tumor cells (ThTCs) were able to eliminate glioblastoma tumors in mice by inducing cancer cell apoptosis, down-regulating cancer-associated fibroblast-expressed platelet-derived growth factor receptor beta, and activating antitumor immune cell trafficking and antigen-specific T cell activation signaling. This approach showed efficacy in various cancer models and maintained safety through the use of a double kill-switch.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Baoshi Yuan, Kexin Shi, Juanmin Zha, Yujia Cai, Yue Gu, Kai Huang, Wenchang Yue, Qiaocheng Zhai, Ning Ding, Wenyan Ren, Weiqi He, Ying Xu, Tao Wang
Summary: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, but chemoresistance limits the efficacy of conventional therapy. This study identified nuclear receptor modulators that inhibit osteosarcoma growth by regulating the PI3K/AKT/mTOR and ERK/mTOR pathways, suggesting a potential therapeutic strategy.
CELL DEATH & DISEASE
(2023)
Article
Chemistry, Multidisciplinary
Kai-li Hao, Qiao-cheng Zhai, Yue Gu, Yue-qiu Chen, Ya-ning Wang, Rui Liu, Shi-ping Yan, Ying Wang, Yu-fang Shi, Wei Lei, Zhen-ya Shen, Ying Xu, Shi-jun Hu
Summary: In this study, researchers disrupted the function of the suprachiasmatic nucleus (SCN) in mice and found that it played a significant role in promoting cardiac repair after myocardial infarction (MI). The study showed that SCN disruption led to the promotion of angiogenesis, reduction of cardiac fibrosis, and altered gene expression in the heart related to inflammatory response and cytokine-cytokine receptor interaction. Additionally, exposure to a desynchronizing condition (constant light) had similar protective effects, suggesting that the effect was mediated by the SCN itself and not by the self-sustained molecular clock.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Biotechnology & Applied Microbiology
Hirotaka Fudaba, Hiroaki Wakimoto
Summary: Oncolytic viruses (OVs) are innovative therapeutic approach for treating malignant brain tumors, featuring unique mechanisms of action. The recent conditional approval of oncolytic herpes simplex virus G47 Delta as a therapeutic for malignant brain tumors is a significant milestone in the field of neuro-oncology.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2023)
Editorial Material
Oncology
Christian Migliarese, Hiroaki Wakimoto
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Biochemical Research Methods
Joana Rita Oliveira Faria Marques, Patricia Gonzalez-Alva, Ruby Yu-Tong Lin, Beatriz Ferreira Fernandes, Akhilanand Chaurasia, Nileshkumar Dubey
Summary: Cancer treatment development is complex due to tumor heterogeneity and inter-patient variations. Traditional 2D cell culture is insufficient to mimic tumor-specific architecture, while 3D culture techniques and bioprinting have shown promise in bridging the gap.
Article
Multidisciplinary Sciences
Yan Zhang, Chi Yan Wong, Carine Z. J. Lim, Qingchang Chen, Zhonglang Yu, Auginia Natalia, Zhigang Wang, Qing You Pang, See Wee Lim, Tze Ping Loh, Beng Ti Ang, Carol Tang, Huilin Shao
Summary: Current technologies to subtype glioblastoma (GBM) rely on invasive brain biopsies. In this study, the authors develop a digital platform called EZ-READ to detect and characterize GBM using circulating RNAs in extracellular vesicles. The platform utilizes an RNA-responsive transducer to convert and enhance signals from rare RNA targets, allowing for programmable and reliable RNA detection directly in blood samples. When evaluated clinically, the EZ-READ platform shows promising results for accurate blood-based diagnosis and subtyping of GBM.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Andrea Schmidts, Ambike A. Srivastava, Rishab Ramapriyan, Stefanie R. Bailey, Amanda A. Bouffard, Daniel P. Cahill, Bob S. Carter, William T. Curry, Gavin P. Dunn, Matthew J. Frigault, Elizabeth R. Gerstner, Jack Y. Ghannam, Michael C. Kann, Rebecca C. Larson, Mark B. Leick, Brian Nahed, Leland G. Richardson, Irene Scarfo, Jing Sun, Hiroaki Wakimoto, Marcela Maus, Bryan D. Choi
Summary: TanCART, a novel dual-specific tandem CAR T cell targeting EGFRvIII and IL-13R alpha 2, has shown enhanced cytotoxicity against heterogeneous GBM tumors, including patient-derived xenografts. Dual antigen engagement is necessary for achieving long-term, complete, and durable responses in orthotopic murine models. These findings support the development of multi-specific CAR T cells for GBM and other cancers.
NEURO-ONCOLOGY ADVANCES
(2023)