Article
Multidisciplinary Sciences
Jan M. Suski, Nalin Ratnayeke, Marcin Braun, Tian Zhang, Vladislav Strmiska, Wojciech Michowski, Geylani Can, Antoine Simoneau, Konrad Snioch, Mikolaj Cup, Caitlin M. Sullivan, Xiaoji Wu, Joanna Nowacka, Timothy B. Branigan, Lindsey R. Pack, James A. DeCaprio, Yan Geng, Lee Zou, Steven P. Gygi, Johannes C. Walter, Tobias Meyer, Piotr Sicinski
Summary: CDC7 is dispensable for cell division, while CDK1 is active during G1/S transition and performs functionally redundant roles with CDC7.
Review
Microbiology
Boris Bogdanow, Quang Vinh Phan, Luder Wiebusch
Summary: Cytomegaloviruses induce significant changes in cell cycle regulation to enable replication of their DNA genomes. They establish a unique cell cycle arrest at the G(1)/S transition, while activating S phase-specific gene expression and nucleotide metabolism. Despite similarities in cell cycle regulation between human and murine CMVs, there are considerable differences in viral cell cycle effectors and mechanisms of action.
Article
Multidisciplinary Sciences
Brian DeVeale, Leqian Liu, Ryan Boileau, Jennifer Swindlehurst-Chan, Bryan Marsh, Jacob W. Freimer, Adam Abate, Robert Blelloch
Summary: This study reveals the cell cycle structure of pluripotent embryonic stem cells and the relationship between G1/S restriction point, gene expression, and cellular differentiation. By genetically manipulating G1/S restriction point regulators miR-302 and P27, the researchers found that they can accelerate or delay the onset of phasic gene expression in mouse embryos. Additionally, loss of miR-302-mediated p21 or p27 suppression expedites embryonic stem cell differentiation, while a mutated Cyclin E blocks it. These findings provide new insights into our understanding of cellular differentiation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Pooya Naseri-Nosar, Maciej T. Nogalski, Thomas Shenk
Summary: Following human cytomegalovirus (HCMV) infection, the aryl hydrocarbon receptor (AhR) is activated and alters the levels of numerous RNAs, including those related to cell cycle progression. AhR knockdown alleviates the G1/S cell cycle block in HCMV-infected fibroblasts, providing mechanistic insight into the virus-host cell interaction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Yiming Lei, Xuan Xu, Huiling Liu, Lingjun Chen, Haoxiong Zhou, Jie Jiang, Yidong Yang, Bin Wu
Summary: The protein ARBB1 plays a critical role in HBV-related hepatocellular carcinoma by modulating autophagy and the CDKN1B-CDK2-CCNE1-E2F1 axis, suggesting it may be a potential therapeutic target for HCC.
Article
Biochemistry & Molecular Biology
Gabriel S. Matos, Juliana B. Madeira, Caroline Mota Fernandes, Deveney Dasilva, Claudio A. Masuda, Maurizio Del Poeta, Monica Montero-Lomeli
Summary: The SBF complex plays a crucial role in sphingolipid homeostasis regulation, influencing the transcription of key enzymes related to LCBs and ceramides synthesis during the cell cycle, with a peak at the G1/S phase. Deletion of SWI4 affects sphingolipid levels throughout the cell cycle progression and induces partial arrest at the G2/M phase.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Engineering, Multidisciplinary
Nimet Ilke Akcay, Benedek Nagy, Sukru Tuzmen
Summary: Reaction Systems modeling is a compact, discrete, and qualitative method for modeling dynamic systems, including biochemical systems. In this paper, the G1/S checkpoint of the human cell cycle was modeled using Reaction Systems, which is essential in understanding tumor formation. Modeling discrete dynamic systems with Reaction Systems offers advantages such as simplicity, determinism, and ease of simulation without the need for specific software packages.
ACTA POLYTECHNICA HUNGARICA
(2021)
Article
Medicine, Research & Experimental
Shumei Kato, Ryosuke Okamura, Jacob J. Adashek, Noor Khalid, Suzanna Lee, Van Nguyen, Jason K. Sicklick, Razelle Kurzrock
Summary: The study investigated clinical outcomes of patients with G(1)/S phase cell-cycle alterations receiving CDK4/6 inhibitor-based therapy, showing that higher proportion of matched tumor alterations was associated with longer progression-free survival and higher rates of stable disease or objective response.
Article
Oncology
Yaoyao Gu, Xiaoxiao Hu, Xiaowei Liu, Cheng Cheng, Kai Chen, Yeming Wu, Zhixiang Wu
Summary: High expression of MCM6 is associated with advanced tumor stage, high risk, and poor prognosis in neuroblastoma. Inhibition of MCM6 significantly impairs neuroblastoma cell proliferation, migration, and invasion. MCM6 is considered a driver of G1/S cell cycle progression and a potential therapeutic target in neuroblastoma.
Article
Cell Biology
Indra A. Shaltiel, Alba Llopis, Melinda Aprelia, Rob Klompmaker, Apostolos Menegakis, Lenno Krenning, Rene H. Medema
Summary: Most Cdks are redundant for normal cell division, but become essential for S-phase entry after DNA damage in G1. In damaged cells, high levels of Cdk4/6 activity are required to inactivate pocket proteins and APC/C-Cdh1 to promote the transition from G1 to S phase.
Article
Biochemistry & Molecular Biology
Diego Lastra, Maribel Escoll, Antonio Cuadrado
Summary: This study explores the involvement of transcription factor NRF2 in the cell division cycle and finds that NRF2 levels are highest during S phase entry and lowest during mitosis. NRF2 depletion leads to G1 and M arrest and affects key cell cycle regulators.
Article
Cell Biology
Jin-Yu Liu, Ya-Jing Chen, Huan-Hui Feng, Zhan-Li Chen, Yun-Long Wang, Jin-E Yang, Shi-Mei Zhuang
Summary: The study reveals that SNHG17 interacts with LRPPRC to enhance c-Myc expression, accelerate G1/S transition and cell proliferation, promoting tumor growth. High levels of SNHG17 or LRPPRC are associated with lower survival rates in HCC patients.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Jin-E Yang, Wang-Jing Zhong, Jin-Feng Li, Ying-Ying Lin, Feng-Ting Liu, Hao Tian, Ya-Jing Chen, Xiao-Yu Luo, Shi-Mei Zhuang
Summary: In this study, a novel micropeptide named SMIM30, encoded by the sORF on LINC00998, was discovered. SMIM30 was found to be localized on the membranes of the endoplasmic reticulum and mitochondria, and it played a role in promoting cell proliferation in hepatoma cells. By regulating the intracellular calcium level, SMIM30 enhanced SERCA activity and reduced cytosolic calcium level, leading to the promotion of G1/S phase transition and cell proliferation.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Simon Gemble, Rene Wardenaar, Kristina Keuper, Nishit Srivastava, Maddalena Nano, Anne-Sophie Mace, Andrea E. Tijhuis, Sara Vanessa Bernhard, Diana C. J. Spierings, Anthony Simon, Oumou Goundiam, Helfrid Hochegger, Matthieu Piel, Floris Foijer, Zuzana Storchova, Renata Basto
Summary: This study reveals that human cells experience high levels of DNA damage during DNA replication in the first S phase following tetraploidy induction. These damages are caused by protein shortage during the G1/S transition, resulting in inaccurate DNA replication. These findings provide an explanation for the genetic instability landscape that favors tumorigenesis after tetraploidization.
Article
Chemistry, Medicinal
Ga-Eun Lee, Dohyun Jeung, Weidong Chen, Jiin Byun, Joo Young Lee, Han Chang Kang, Hye Suk Lee, Dae Joon Kim, Jin-Sung Choi, Cheol-Jung Lee, Hyun-Jung An, Yong-Yeon Cho
Summary: In this study, it was found that FBXO1 binds to E2Fs and induces ubiquitination and degradation of E2Fs. The residues Arg/Ile and R/Val in the dimerization domain of E2Fs act as degron motifs for FBXO1. MEK/ERK signaling molecules play a key role in the interaction between FBXO1 and E2Fs and modulate E2F protein turnover. Modulating the stability of E2Fs through the FBXO1-E2Fs axis can delay G(1)/S cell cycle transition and inhibit cancer cell proliferation.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Endocrinology & Metabolism
Hisashi Ideno, Kazuhisa Nakashima, Koichiro Komatsu, Ryoko Araki, Masumi Abe, Yoshinori Arai, Hiroshi Kimura, Yoichi Shinkai, Makoto Tachibana, Akira Nifuji
Article
Biochemistry & Molecular Biology
Vasia Samantha Sykioti, Mantia Karampetsou, Ioanna Chalatsa, Alexia Polissidis, Iacovos P. Michael, Marina Pagaki-Skaliora, Andras Nagy, Evangelia Emmanouilidou, Georgia Sotiropoulou, Kostas S. Vekrelli
Summary: The roles of KLK6 in regulating alpha-syn processing and pathology transmission in vivo were investigated using Klk6 knock-out mice. The study showed that KLK6 deletion did not impact alpha-syn accumulation or behavior in mice, and active KLK6 did not affect alpha-syn levels in A53T alpha-syn over-expressing mice, indicating that KLK6 alone may not be sufficient to modulate alpha-syn pathology transmission. These findings suggest implications for using recombinant alpha-syn fibrils in studies of alpha-syn turnover.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mohammed H. Abuwarwar, Alfie T. Baker, Jeffrey Harding, Natalie L. Payne, Andras Nagy, Konstantin Knoblich, Anne L. Fletcher
Summary: T cell immunotherapy is effective for blood-borne cancers and melanoma, but many epithelial tumors show poor response. Cancer-associated fibroblasts (CAFs) are emerging as key players in immunotherapy resistance. Immortalized CAF lines are valuable tools for studying mechanisms of CAF-mediated T cell suppression and developing novel cancer immunotherapy strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Orthopedics
Rahul Gawri, Ryszard Bielecki, Eric W. Salter, Alena Zelinka, Toshikazu Shiba, Graham Collingridge, Andras Nagy, Rita A. Kandel
Summary: Inorganic polyphosphates (polyP) require calcium influx to regulate chondrocyte matrix production, likely through activating calcium signaling pathway. These findings help in the clinical translation of polyP into a therapeutic agent for cartilage repair.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2022)
Article
Neurosciences
Rehnuma Islam, Stasja Drecun, Balazs V. Varga, Ilan Vonderwalde, Ricky Siu, Andras Nagy, Cindi M. Morshead
Summary: Human cortically specified neural precursor cells (cNEPs) derived from ESCs have shown promise in improving motor function following stroke in animal models. While the transplanted cells do not persist long-term, they still support functional recovery, indicating a bystander effect rather than cell replacement.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Isabelle R. de Luzy, Kevin C. L. Law, Niamh Moriarty, Cameron P. J. Hunt, Jennifer C. Durnall, Lachlan H. Thompson, Andras Nagy, Clare L. Parish
Summary: This study used a human pluripotent stem cell line carrying a FailSafe suicide gene to selectively ablate proliferative cells in a Parkinsonian model, resulting in improved safety and purity of neural grafts. Activation of the suicide gene post-transplantation led to smaller grafts without affecting dopamine neuron yield, innervation capacity, or motor deficits reversal, demonstrating the potential of a suicide gene-based system to enhance the standardization and safety of stem cell-derived grafts.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Marion Mesnieres, Anna-Marei Bohm, Nicolas Peredo, Dana Trompet, Roger Valle-Tenney, Manmohan Bajaj, Nikky Corthout, Elena Nefyodova, Ruben Cardoen, Pieter Baatsen, Sebastian Munck, Andras Nagy, Jody J. Haigh, Satish Khurana, Catherine M. Verfaillie, Christa Maes
Summary: The balanced local crosstalk within the skeletal niche is crucial for the successful settlement of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow, with overproduction of VEGF by osteoprogenitor cells impacting stromal-vessel interface and vascular architecture, resulting in impaired HSPC homing and survival. These findings highlight potential targets for improving stem cell therapies, as similar osteo-angiogenic niche changes are induced by irradiation in adult mice.
Article
Multidisciplinary Sciences
Yanxing Wei, Tianyu Wang, Lishi Ma, Yanqi Zhang, Yuan Zhao, Kathryn Lye, Lu Xiao, Chunlin Chen, Zhijian Wang, Yanlin Ma, Xiaohua Zhou, Fei Sun, Weili Li, Caroline Dunk, Siliang Li, Andras Nagy, Yanhong Yu, Guangjin Pan, Stephen J. Lye, Yongli Shan
Summary: This passage discusses the successful generation of trophoblast stem cells from primed human pluripotent stem cells, with BMP4 playing a significant role in the process. The derived TSCs are similar to blastocyst-derived hTSCs in various characteristics, and the chromatin accessibility dynamics and histone modifications involved in specifying hPSC-derived TSCs are defined. Additionally, knockout of H3K27 methyltransferases (EZH1/2) is shown to increase the efficiency of hTSC derivation from primed hPSCs.
Article
Cell & Tissue Engineering
Danni Lyu, Lifang Zhang, Zhenwei Qin, Shuang Ni, Jiayong Li, Bing Lu, Shengjie Hao, Qiaomei Tang, Houfa Yin, Zhijian Chen, Yong-Bin Yan, Junfeng Ji, Jiliang He, Andras Nagy, Qiuli Fu, Ke Yao
Summary: This study established a human congenital cataract in vitro model by differentiating patient-specific induced pluripotent stem cells (iPSCs) into regenerated lenses, which recapitulated the clinical manifestations and protein aggregation characteristics of patients' cataracts.
NPJ REGENERATIVE MEDICINE
(2021)
Article
Multidisciplinary Sciences
Balazs V. Varga, Maryam Faiz, Huijuan Yang, Helena Pivonkova, Shangbang Gao, Gabriel Khelifi, Emma Linderoth, Mei Zhen, Ragnhildur Thora Karadottir, Samer M. Hussein, Andras Nagy
Summary: This study identifies signals that regulate the division of human neural stem cells and their ability to generate cortical neurons and glia. Understanding these mechanisms is vital for the development of regenerative and cell-based therapeutic approaches for neurological conditions.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Judith Elbaz, Mira C. Puri, Maryam Faiz, K. W. Annie Bang, Lena Nguyen, Bar Makovoz, Marina Gertsenstein, Samer M. Hussein, Peter W. Zandstra, Laurent Briollais, Nika Shakiba, Andras Nagy
Summary: This study reports the development of two efficient transgenic mouse lines for rapid reprogramming of various fetal and adult tissue-derived somatic cells. These mouse lines serve as powerful tools for exploring the sources of variability in reprogramming and the mechanistic underpinnings of efficient reprogramming systems.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell & Tissue Engineering
Eric D. Jong, Sabiha Hacibekiroglu, Lily Guo, Evan Sawula, Biao Li, Chengjin Li, Margaret T. Ho, Molly S. Shoichet, Valerie A. Wallace, Andras Nagy
Summary: A combined cell and gene therapy was developed for the treatment of retinitis pigmentosa (RP). Human embryonic stem cells (hESCs) were genetically engineered to differentiate into retinal pigment epithelium (hRPE) cells, which were used to protect and preserve photoreceptor cells in mouse models. This study reveals the potential of this therapy for RP treatment and the possibility of using hRPE cells for long-term delivery of therapeutic biologics.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Cell & Tissue Engineering
Evan Sawula, Shane Miersch, Eric D. Jong, Chengjin Li, Fang-Yu Chou, Jean Kit Tang, Reza Saberianfar, Jeffrey Harding, Sachdev S. Sidhu, Andras Nagy
Summary: By combining cell and mAb engineering, we have developed a safe and universal cell therapy that can continuously secrete neutralizing antibodies, providing sustained immune protection against current and future viral pathogens of public health significance.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Developmental Biology
Luis Covarrubias, Jose-Angel Martinez-Sarmiento, Concepcion Valencia, Andras Nagy, David Hernandez-Garcia
Summary: Regulatory pluripotency factors levels influence reprogramming initiation and PSC maintenance in vitro without affecting their differentiation potential in vivo.
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
(2021)