Article
Multidisciplinary Sciences
Liu Yang, Haiyan Yang, Yunxiang Chu, Yunhao Song, Lidan Ding, Bingtao Zhu, Wanli Zhai, Xuning Wang, Yanshen Kuang, Fangli Ren, Baoqing Jia, Wei Wu, Xiongjun Ye, Yinyin Wang, Zhijie Chang
Summary: This study reveals the essential role of CREPT in maintaining murine intestinal stem cells, with its deficiency impairing cell proliferation and regeneration. The downregulation of Wnt signaling due to CREPT deletion is identified as a key mechanism affecting ISC function.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jonathan Ribeiro, Gerry P. Crossan
Summary: Recycling and de-novo deposition of histones during DNA replication is coordinated by histone chaperones. Here, we demonstrate the role of a germ cell specific histone chaperone, GCNA, in the maintenance of undifferentiated spermatogonia (USGs) in mice. Our findings provide a mechanistic basis for male infertility caused by GCNA mutations.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Shengyuan Zhao, Rodan Devega, Aaliyah Francois, Dawit Kidane
Summary: ALKBH6, an α-ketoglutarate-dependent dioxygenase, plays a crucial role in preventing alkylating DNA damage and decreasing genomic instability in pancreatic cancer cells. Overexpression of ALKBH6 has been shown to improve survival outcomes in patients with pancreatic cancer.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Lin Wang, Mande Xue, Huairen Zhang, Lijun Ma, Danhua Jiang
Summary: Plant TONSOKU (TSK) and its animal ortholog TON-SOKU-like (TONSL) play a crucial role in maintaining chromatin stability during DNA replication. TSK interacts with histone modifiers and Polycomb proteins to preserve repressive chromatin modifications. TSK is specifically involved in a critical period of time following DNA replication to ensure the preservation of chromatin states.
Article
Multidisciplinary Sciences
Ines C. Osma-Garcia, Dunja Capitan-Sobrino, Mailys Mouysset, Sarah E. Bell, Manuel Lebeurrier, Martin Turner, Manuel D. Diaz-Munoz
Summary: The RNA binding protein HuR plays a crucial role in supporting germinal centre (GC) responses by promoting Myc-dependent transcription and influencing the expression and splicing patterns of genes involved in GC B cell proliferation and Ig somatic hypermutation. Additionally, HuR modulates mRNA splicing and abundance for cell cycle progression, and protects GC B cells from DNA damage and cell death.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Aiting Wang, Lei Ding, Zhongqiu Wu, Rui Ding, Xiao-Lu Teng, Feixiang Wang, Zhilin Hu, Lei Chen, Xiaoyan Yu, Qiang Zou
Summary: This study demonstrates that the E3 ubiquitin ligase ZFP91 promotes autophagy activation in regulatory T cells, maintaining their metabolic programming and functional integrity. Deletion of Zfp91 in T cells leads to dysfunction and exacerbates colonic inflammation and inflammation-driven colon cancer. TCR-triggered autophagy induction relies on T cell-derived ZFP91 to restrict hyperglycolysis for cell homeostasis maintenance.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Letter
Oncology
Lingyu Wei, Can Liu, Jia Wang, Xiang Zheng, Qiu Peng, Qiurong Ye, Zailong Qin, Zhengshuo Li, Xiaoyue Zhang, Yangge Wu, Yuqing Wen, Xuemei Zhang, Qun Yan, Jian Ma
Summary: Lactoferrin is essential for early B cell development in mice, with lactoferrin deficiency leading to a blockade in early B cell development, potentially mediated through signaling pathways, transcription factors, and alterations in bone marrow microenvironment.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Mayura Wagle, Stephin J. Vervoort, Madison J. Kelly, Willem Van der Byl, Timothy J. Peters, Ben P. Martin, Luciano G. Martelotto, Simone Nuessing, Kelly M. Ramsbottom, James R. Torpy, Deborah Knight, Sinead Reading, Kevin Thia, Lisa A. Miosge, Debbie R. Howard, Renee Gloury, Sarah S. Gabriel, Daniel T. Utzschneider, Jane Oliaro, Jonathan D. Powell, Fabio Luciani, Joseph A. Trapani, Ricky W. Johnstone, Axel Kallies, Christopher C. Goodnow, Ian A. Parish
Summary: Chronic antigenic stimulation induces the expression of EGR2, which in turn affects the epigenetic and transcriptional identity of exhausted T cells.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Faming Wang, Dongya Cui, Qingyun Zhang, Yingying Shao, Baijiao Zheng, Liling Chen, Yao Luo, Liudi Yuan, Demin Wang
Summary: Long non-coding RNA Gme00492 plays a significant role in B-cell development, particularly in the development of marginal zone B cells. It interacts with CTBP1 to target it for ubiquitination and degradation, impacting Notch2 signaling pathway, and ultimately affecting the development of B cells.
Article
Medicine, Research & Experimental
Annalisa D'Avola, Nathalie Legrave, Mylene Tajan, Probir Chakravarty, Ryan L. Shearer, Hamish W. King, Katarina Kluckova, Eric C. Cheung, Andrew J. Clear, Arief S. Gunawan, Lingling Zhang, Louisa K. James, James MacRae, John G. Gribben, Dinis P. Calado, Karen H. Vousden, John C. Riches
Summary: The synthesis of serine from glucose plays a crucial role in cellular proliferation and is important in germinal center biology. This study shows that upregulation of serine synthesis pathway is a metabolic hallmark of B cell activation and the germinal center reaction, and inhibiting the key enzyme PHGDH leads to defective germinal formation and impaired antibody production. Furthermore, overexpression of enzymes involved in serine synthesis is characteristic of germinal center B cell-derived lymphomas, and inhibiting PHGDH can induce apoptosis in lymphoma cells, reducing disease progression.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Qingnan Tian, Yujia Sun, Tingting Gao, Jiaxin Li, Huimin Fang, Shoutao Zhang
Summary: SUMOylation and ubiquitylation are crucial processes in eukaryotic biology, with Djubc9 and Djnedd4L identified as important factors in head regeneration in planarians through RNA-seq analysis. RNA interference experiments confirmed their roles in stem cell maintenance and regeneration processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Peifeng Li, Jia Chai, Zi Chen, Yang Liu, Jie Wei, Yixiong Liu, Danhui Zhao, Jing Ma, Kaijing Wang, Xia Li, Yang Shao, Li Gong, Wei Zhang, Shuangping Guo, Qingguo Yan, Mingyang Li, Linni Fan, Zhe Wang
Summary: The study analyzed whole-exome sequencing data of 25 GI-DLBCL patients, identifying genetic oncogenic mutations including TP53, MUC16. GI-DLBCL shows different genetic mutations compared to other DLBCL types, which may influence its clinicopathological characteristics.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Tobit D. Steinmetz, Ursula Schloetzer-Schrehardt, Abigail Hearne, Wolfgang Schuh, Jens Wittner, Sebastian R. Schulz, Thomas H. Winkler, Hans-Martin Jaeck, Dirk Mielenz
Summary: TFG is upregulated during differentiation of B cells into plasma cells, regulating ER structure and autophagy flux. Loss of TFG disrupts ER structure, leading to increased ER stress gene expression and decreased autophagy flux. TFG is a survival factor that alleviates ER stress through supporting autophagy flux in activated B cells and plasma cells.
Article
Immunology
Hyunju Oh, Jingyao Zhao, Yenkel Grinberg-Bleyer, Thomas S. Postler, Pingzhang Wang, Sung-Gyoo Park, Raul Rabadan, Matthew S. Hayden, Sankar Ghosh
Summary: This study demonstrates the essential role of PDK1 in both T cell activation and Treg cell suppressive activity, with PDK1 regulating Treg cell gene expression and suppressor function primarily through the NF-κB pathway.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Jiao-Xiang Wu, Kun-Yan He, Zhuang-Zhuang Zhang, Yu-Lan Qu, Xian-Bin Su, Yi Shi, Na Wang, Lan Wang, Ze-Guang Han
Summary: The liver-specific zona pellucida domain-containing protein (LZP) deficiency inhibits VLDL secretion, leading to hepatic TG accumulation and lower serum TG levels, primarily due to decreased levels of apoB protein.
Article
Biochemical Research Methods
Hendrik A. Messal, Jorge Almagro, May Zaw Thin, Antonio Tedeschi, Alessandro Ciccarelli, Laura Blackie, Kurt I. Anderson, Irene Miguel-Aliaga, Jacco van Rheenen, Axel Behrens
Summary: The FLASH technique is a quick and customizable method for molecular phenotyping of intact tissue volumes. It enables detection of a multitude of antigens in whole mouse organs and embryos, human biopsies, organoids, and Drosophila. FLASH allows for epithelial marker retrieval and immunolabeling, and preserves sample architecture for subsequent histopathological analysis.
Article
Oncology
Ruochen Jia, Leon Kutzner, Anna Koren, Kathrin Runggatscher, Peter Majek, Andre C. Mueller, Michael Schuster, Christoph Bock, Joanna I. Loizou, Stefan Kubicek, Robert Kralovics
Summary: Mutations of calreticulin (CALR) are the second most common driver mutations in essential thrombocythemia and primary myelofibrosis. A study identified synthetic lethality with compounds targeting the ATR-CHK1 pathway in CALR mutated cells, highlighting the potential therapeutic target in CALR mutated hematopoietic cells. CHK1 inhibitors induced replication stress and S-phase cell cycle arrest in CALR mutated cells, demonstrating specificity for the oncogenic activation by the mutant CALR.
BLOOD CANCER JOURNAL
(2021)
Article
Medicine, Research & Experimental
Jose Gonzalez-Martinez, Andrzej W. Cwetsch, Diego Martinez-Alonso, Luis R. Lopez-Sainz, Jorge Almagro, Anna Melati, Jesus Gomez, Manuel Perez-Martinez, Diego Megias, Jasminka Boskovic, Javier Gilabert-Juan, Osvaldo Grana-Castro, Alessandra Pierani, Axel Behrens, Sagrario Ortega, Marcos Malumbres
Summary: The study reveals that defects in certain genes during development can lead to mild MCPH symptoms, while the lack of centrosome or centriole regulators can cause chromosomal instability in neural progenitor cells.
Article
Medicine, Research & Experimental
E. Josue Ruiz, Linxiang Lan, Markus Elmar Diefenbacher, Eva Madi Riising, Clive Da Costa, Atanu Chakraborty, Joerg D. Hoeck, Bradley Spencer-Dene, Gavin Kelly, Jean-Pierre David, Emma Nye, Julian Downward, Axel Behrens
Summary: In a mouse model of K-RasG12D-induced lung adenocarcinoma, deletion or mutation of c-Jun unexpectedly increased lung tumor burden, while the Jun family member JunD was found to be crucial in JNK signaling and Ras-induced lung cancer in the absence of c-Jun.
Article
Cell Biology
Huafu Li, Chunming Wang, Linxiang Lan, Wenhui Wu, Ian Evans, E. Josue Ruiz, Leping Yan, Zhijun Zhou, Joaquim M. Oliveira, Rui L. Reis, Zhenran Hu, Wei Chen, Axel Behrens, Yulong He, Changhua Zhang
Summary: The study identified PARP1 gene as a key mediator of OXA resistance and proposed a combination therapy strategy using OXA and Olaparib to target this resistance mechanism. The results showed significant correlation between PARP1 expression and OXA resistance, with genetic manipulation confirming its role in mediating resistance. The combination therapy effectively inhibited the growth and viability of OXA-resistant organoids both in vivo and in vitro.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Huafu Li, Chunming Wang, Linxiang Lan, Leping Yan, Wuguo Li, Ian Evans, E. Josue Ruiz, Qiao Su, Guangying Zhao, Wenhui Wu, Haiyong Zhang, Zhijun Zhou, Zhenran Hu, Wei Chen, Joaquim M. Oliveira, Axel Behrens, Rui L. Reis, Changhua Zhang
Summary: In this study, the researchers investigated the mechanism of oxaliplatin resistance in gastric cancer using in vitro human gastric cancer organoids and oxaliplatin-resistant cell lines, as well as in vivo tumorigenicity experiments. They found that CD133+ stem cell-like cells are the main subpopulation associated with resistance, and that the gene PARP1 plays a central role in mediating this resistance. The researchers discovered that PARP1 can effectively repair DNA damage caused by oxaliplatin by activating the base excision repair pathway, leading to the development of drug resistance. They also found that CD133+ cells exhibit increased expression of the mRNA modification N6-methyladenosine (m6A) and its writer METTL3, which enhances the stability of PARP1 and contributes to its DNA damage repair ability. Overall, this study demonstrates that m6A methyltransferase METTL3 promotes oxaliplatin resistance in CD133+ gastric cancer stem cells by increasing PARP1 mRNA stability and base excision repair activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Matthew R. J. Mason, Susan van Erp, Kim Wolzak, Axel Behrens, Gennadij Raivich, Joost Verhaagen
Summary: The regeneration-associated gene expression program is crucial for axon re-growth in injured peripheral neurons. Jun, a transcription factor, plays an important role in regulating this program by upregulating gene expression and promoting cell regeneration while inhibiting plasticity response.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biology
E. Josue Ruiz, Adan Pinto-Fernandez, Andrew P. Turnbull, Linxiang Lan, Thomas M. Charlton, Hannah C. Scott, Andreas Damianou, George Vere, Eva M. Riising, Clive Da Costa, Wojciech W. Krajewski, David Guerin, Jeffrey D. Kearns, Stephanos Ioannidis, Marie Katz, Crystal McKinnon, Jonathan O'Connell, Natalia Moncaut, Ian Rosewell, Emma Nye, Neil Jones, Claire Heride, Malte Gersch, Min Wu, Christopher J. Dinsmore, Tim R. Hammonds, Sunkyu Kim, David Komander, Sylvie Urbe, Michael J. Clague, Benedikt M. Kessler, Axel Behrens
Summary: Lung squamous cell carcinoma (LSCC) is a significant global health burden with limited treatment options, but inhibition of USP28 can lead to tumor regression.
Article
Multidisciplinary Sciences
Jessica K. Nelson, May Zaw Thin, Theodore Evan, Steven Howell, Mary Wu, Bruna Almeida, Nathalie Legrave, Duco S. Koenis, Gabriela Koifman, Yoichiro Sugimoto, Miriam Llorian Sopena, James MacRae, Emma Nye, Michael Howell, Ambrosius P. Snijders, Andreas Prachalias, Yoh Zen, Debashis Sarker, Axel Behrens
Summary: This study reveals that the deubiquitinating enzyme USP25 promotes growth and survival of pancreatic ductal adenocarcinoma (PDAC) by stabilizing and regulating the transcriptional activity of HIF-1 protein. PDAC is characterized by a severely hypoxic microenvironment, and inhibition of USP25 impairs HIF-1 activity and induces cell death in the tumor core. The USP25/HIF-1α axis may be a potential therapeutic target for PDAC.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Linxiang Lan, Theodore Evan, Huafu Li, Aasia Hussain, E. Josue Ruiz, May Zaw Thin, Rute M. M. Ferreira, Hari Ps, Eva M. Riising, Yoh Zen, Jorge Almagro, Kevin W. Ng, Pablo Soro-Barrio, Jessica Nelson, Gabriela Koifman, Joana Carvalho, Emma L. Nye, Yulong He, Changhua Zhang, Anguraj Sadanandam, Axel Behrens
Summary: This study identifies BMP inhibitor GREM1 as a key regulator of cellular heterogeneity in pancreatic cancer. Continuous activity of GREM1 is required to maintain the stability of the epithelial PDAC subpopulations, while high activity of GREM1 can revert the mesenchymal fate of PDAC cells. By inhibiting the expression of epithelial-mesenchymal transition transcription factors, GREM1 restricts the epithelial-mesenchymal plasticity of pancreatic cancer cells.
Article
Multidisciplinary Sciences
Teodora Manea, Jessica Kristine Nelson, Cristina Maria Garrone, Karin Hansson, Ian Evans, Axel Behrens, Rocio Sancho
Summary: Understanding the role of NGN3 in beta-cell development is crucial for developing therapies for diabetes. This study identifies USP7 as a key regulator of NGN3 stability and shows that it is necessary for endocrine development and beta-cell differentiation. Inhibition of USP7 reduces NGN3 expressing progenitor cell numbers and impairs beta-cell differentiation. The findings suggest that targeting the USP7-NGN3 axis could be a therapeutic strategy for generating functional beta cells.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Sergio Pedraza-Arevalo, Ana-Maria Cujba, Mario Enrique Alvarez-Fallas, Rocio Sancho
Summary: This study presents a protocol for differentiating hiPSCs into pancreatic progenitor organoids and beta-like cells. The organoids obtained from this protocol contain beta, delta, and alpha cells.
Review
Oncology
Jorge Almagro, Hendrik A. Messal, Alberto Elosegui-Artola, Jacco van Rheenen, Axel Behrens
Summary: The 3D architecture of tissues bearing tumors has significant impacts on the mechanical microenvironment of cancer, the accessibility of stromal cells, and the routes of invasion. Various forces from cancer cells, host tissue, and the molecular and cellular microenvironment modulate the morphology and malignant potential of the tumor through mechanical, biochemical, genetic, and epigenetic cues. Recent studies have revealed how tissue architecture influences cancer biology and progression.
Article
Cell Biology
Huafu Li, Chunming Wang, Linxiang Lan, Axel Behrens, Mona Tomaschko, Josue Ruiz, Qiao Su, Guangying Zhao, Cheng Yuan, Xing Xiao, Bo Li, Leping Yan, Wang Wu, Wuguo Li, Junzong Chen, Yulong He, Changhua Zhang
Summary: EMT plays a crucial role in the aggressiveness and metastasis of gastric cancer, especially in the infiltration of NK cells into tumor cells. Vinculin expression is closely related to cancer aggressiveness and distant metastasis, affecting patient survival prognosis. Additionally, VCL can influence EMT and tumor immunity by regulating EPCAM gene expression.
Review
Oncology
Anna Schrempf, Jana Slyskova, Joanna Loizou
Summary: Targeted cancer therapies focusing on POLQ, an error-prone translesion polymerase involved in DNA repair, represent a promising approach in personalized cancer treatment. Inhibition of POLQ, currently under development, shows potential for more effective cancer therapies in the future.