Article
Multidisciplinary Sciences
Zhifan Xie, Xian-Hu Ma, Qiu-Fang Bai, Jie Tang, Jian-He Sun, Fei Jiang, Wei Guo, Chen-Ma Wang, Rui Yang, Yin-Chuan Wen, Fang-Yuan Wang, Yu-Xia Chen, Hai Zhang, David Z. He, Matthew W. Kelley, Shiming Yang, Weiping J. Zhang
Summary: Very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral nonsensory region. ZBTB20 is abundantly expressed in the developing and mature cochlear nonsensory epithelial cells and is essential for cochlear terminal differentiation and maturation and hearing. The absence of ZBTB20 causes profound deafness and various structural defects in the cochlear epithelium.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Endi K. Santosa, Hyunu Kim, Timo Rueckert, Jean-Benoit Le Luduec, Aamna J. Abbasi, Claire K. Wingert, Lila Peters, Joe N. Frost, Katharine C. Hsu, Chiara Romagnani, Joseph C. Sun
Summary: NK cells and adaptive CD8+ T cells share transcriptional and epigenetic programs. This study identifies IRF4 as a signal integrator for coordinating the response of NK cells during cytomegalovirus infection. Loss of IRF4 affects the expansion and differentiation of virus-specific NK cells, partly due to impaired nutrient uptake.
Article
Oncology
Alboukadel Kassambara, Laurie Herviou, Sara Ovejero, Michel Jourdan, Coraline Thibaut, Veronika Vikova, Philippe Pasero, Olivier Elemento, Jerome Moreaux
Summary: This study used RNA sequencing to analyze the temporal gene expression program of human plasma cell differentiation. It identified thousands of differentially expressed genes categorized into four temporal patterns, as well as novel pathways and transcriptional networks potentially relevant to plasma cell differentiation. Additionally, the study experimentally validated the role of a gene, BLM, in regulating cell survival and proliferation during human plasma cell differentiation, providing valuable insights into the underlying mechanisms of this process.
Article
Microbiology
Jillian A. Bristol, Joshua Brand, Makoto Ohashi, Mark R. Eichelberg, Alejandro Casco, Scott E. Nelson, Mitchell Hayes, James C. Romero-Masters, Dana C. Baiu, Jenny E. Gumperz, Eric C. Johannsen, Huy Q. Dinh, Shannon C. Kenney
Summary: This study reveals the differences in gene expression and signaling pathway activation between T1 and T2 EBV strains in human B cells. T2 EBV-infected B cells have more lytic infection, increased B-cell receptor signaling and NFAT activation, and enhanced expression of epithelial-mesenchymal-transition-associated genes. Furthermore, decreased expression of IRF4 contributes to both the latent and lytic phenotypes in T2 EBV-infected B cells.
Article
Cell & Tissue Engineering
Phoebe K. Mondala, Ashni A. Vora, Tianyuan Zhou, Elisa Lazzari, Luisa Ladel, Xiaolin Luo, Youngsoo Kim, Caitlin Costello, A. Robert MacLeod, Catriona H. M. Jamieson, Leslie A. Crews
Summary: In multiple myeloma, the inflammatory and anti-viral pathways play a role in disease progression and the generation of cancer stem cells. The inhibition of interferon regulatory factor 4 (IRF4) using antisense oligonucleotides (ASOs) shows promise in impairing myeloma cell survival and reducing tumor burden in pre-clinical models. Targeting IRF4 may offer a new strategy for preventing myeloma relapse driven by progenitor cells.
Article
Immunology
Sarah L. Cook, Evelyn P. Sievert, Roger Sciammas
Summary: The transcription factor IRF4 is essential for the selection of high-affinity GCBs, with halving Irf4 gene copy number leading to impaired generation of high-affinity cells. This study highlights the continuous role of IRF4 in later phases of the B cell response, promoting productive T follicular helper cell interactions and optimal Blimp-1 expression during GC selection and affinity maturation.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Cell & Tissue Engineering
Padmina Shrestha, Anbalagan Jaganathan, Dhananjay Huilgol, Carlos Ballon, Yon Hwangbo, Alea A. Mills
Summary: Chd5 is an ATP-dependent chromatin remodeler that promotes neuronal differentiation, but its mechanism in neurogenesis is not well understood. Through transcriptional profiling of Chd5 deficient mice, we found that Chd5 regulates neurogenesis by directing stepwise transcriptional changes. Chd5 promotes the expression of Six3, a proneural transcription factor, to repress the non-canonical Wnt ligand Wnt5a during early stages of neurogenesis. This ability of Chd5 to transcriptionally repress neuronal maturation factors is critical for both lineage specification and maturation.
Article
Multidisciplinary Sciences
Jingying Zhou, Huanyu Wang, Ting Shu, Jing Wang, Weiqin Yang, Jingqing Li, Lipeng Ding, Man Liu, Hanyong Sun, John Wong, Paul Bo-san Lai, Shun-Wa Tsang, Simon E. Ward, King-Lau Chow, Joseph Jao-yiu Sung, Alfred Sze-Lok Cheng
Summary: Massive expansion of immature and suppressive myeloid cells is a common feature of malignant solid tumors. Over-expression of cyclin-dependent kinase 20 in hepatocellular carcinoma correlates with reduced patient survival and low immunotherapy responsiveness. Here, we showed that CCRK is upregulated in myeloid cells in tumor-bearing mice and in patients with HCC. Inactivation of Ccrk in myeloid cells confers a mature phenotype and increases IL-12 production, leading to reduced tumor growth and prolonged survival. Mechanistically, CCRK activates STAT3/E4BP4 signaling to induce immunosuppression. Our findings provide insights into MDSC-mediated immunosuppression and offer a potential kinase-target for cancer immunotherapy.
Article
Cell Biology
Weitang Guo, Xin Wang, Bing Lu, Jiaming Yu, Mingxian Xu, Renxuan Huang, Mingzhe Cheng, Meiling Yang, Wei Zhao, Changye Zou
Summary: This study reveals that super-enhancer-driven Max-like protein X (MLX) has an important role in osteosarcoma, and downregulation of MLX not only inhibits tumor growth and metastasis, but also disrupts iron metabolism and induces ferroptosis. These findings provide a novel potential target for the treatment of osteosarcoma, which is to disrupt the redox balance of the tumor by inhibiting SLC7A11.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Wen-Shuai Tang, Li Weng, Xu Wang, Chang-Qin Liu, Guo-Sheng Hu, Shu-Ting Yin, Ying Tao, Ni-Na Hong, Huiling Guo, Wen Liu, Hong-Rui Wang, Tong-Jin Zhao
Summary: The study identified MED20 as a substrate of the anti-obesity CRL4-WDTC1 E3 ubiquitin ligase complex, with its overexpression leading to MED20 degradation. Depletion of MED20 inhibits adipogenesis, while a non-degradable MED20 mutant can restore adipogenesis.
Article
Cell Biology
Olivia Muriel, Laetitia Michon, Wanda Kukulski, Sophie G. Martin
Summary: In the process of cell-cell fusion in walled fission yeast, researchers have discovered marked asymmetries between gametes, with the plasma membrane of h- cells protruding into h+ cells. This asymmetry is relaxed upon fusion, with the formation of ramified fusion pores. This suggests that differential turgor pressure and exocytosis/endocytosis ratios between mating types favor cell-cell fusion.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Takanori Hironaka, Noburo Takizawa, Yuto Yamauchi, Yuma Horii, Michio Nakaya
Summary: This study reveals that the well-developed actin cytoskeleton and expression of drebrin promote cardiac and hepatic fibrosis. Drebrin regulates the expression of fibrosis-related genes, such as collagen, through the myocardin-related transcription factor-serum response factor signaling pathway. Furthermore, drebrin exerts profibrotic effects in liver myofibroblasts by promoting actin cytoskeleton formation and regulating Cthrc1 expression. Importantly, drebrin expression levels increase in human fibrotic heart and liver tissues.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Yali Chen, Juan Liu, Xiaomin Zhang, Ha Zhu, Yujia Wang, Zhiqing Li, Yanfang Liu, Shuo Liu, Shuxun Liu, Nan Li, Kun Chen, Xuetao Cao
Summary: RNA-RBP interaction plays a crucial role in immune regulation and is associated with various immune disorders. This study demonstrates that lncRNA-GM can polarize TH17 differentiation while inhibiting iTreg differentiation by reducing Foxo1 activity. The findings provide mechanistic insights into the interaction between lncRNA and transcription factors in determining T cell subset differentiation during T cell-mediated autoimmune diseases.
Article
Plant Sciences
Mengzhan Li, Chunli Liu, Shelley R. Hepworth, Chaofan Ma, Hong Li, Jia Li, Suo-Min Wang, Hongju Yin
Summary: The study reveals the interaction between SAUR15 and BRI1 receptor and its promoting effect on BR signal transduction in Arabidopsis. SAUR15 drives cell expansion and promotes plant growth and development by directly activating plasma membrane H+-ATPase. This provides new insights into the BR signaling mechanism in plants.
Article
Biochemistry & Molecular Biology
Jason P. Mansell, Aya Tanatani, Hiroyuki Kagechika
Summary: The combination of the new VDR agonist LCA-150 with LPA has synergistic effects on promoting osteoblast maturation, surpassing the efficacy of vitamin D.
Editorial Material
Immunology
Isaak Quast, David Tarlinton
Summary: Immunological memory is crucial for protecting against reinfection, with antibodies produced by B cells playing a key role in this defense mechanism. Understanding how B cell memory is generated, its efficacy, and persistence, particularly in response to SARS-CoV-2, is essential for achieving protective immunity through vaccination.
Article
Multidisciplinary Sciences
Wing Fuk Chan, Hannah D. Coughlan, Jie H. S. Zhou, Christine R. Keenan, Naiara G. Bediaga, Philip D. Hodgkin, Gordon K. Smyth, Timothy M. Johanson, Rhys S. Allan
Summary: The study elucidated the chromosome conformational changes in B lymphocytes as they differentiate into plasma cells, indicating that these changes occur prior to cell division and may guide the gene expression necessary for differentiation.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Andrew D. Foers, Alexandra L. Garnham, Simon Chatfield, Gordon K. Smyth, Lesley Cheng, Andrew F. Hill, Ian P. Wicks, Ken C. Pang
Summary: In rheumatoid arthritis, extracellular vesicles are associated with joint inflammation and destruction. Through sequencing EV miRNAs in synovial fluid from RA patients, differences between joints with high- and low-grade inflammation were identified, suggesting a role in regulating inflammation-related genes. EV miRNAs have the potential to modulate inflammation and contribute to RA pathophysiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Developmental Biology
Zoe L. Grant, Peter F. Hickey, Waruni Abeysekera, Lachlan Whitehead, Sabrina M. Lewis, Robert C. A. Symons, Tracey M. Baldwin, Daniela Amann-Zalcenstein, Alexandra L. Garnham, Gordon K. Smyth, Tim Thomas, Anne K. Voss, Leigh Coultas
Summary: The histone acetyltransferase HBO1 plays a crucial role in blood vessel development, with its impairment leading to defects in developmental sprouting angiogenesis and pathological EC overgrowth in the retinal endothelium. Loss of HBO1 results in an increased abundance of tip cells, hindering efficient tip cell migration and causing EC overcrowding in the retinal sprouting front.
Editorial Material
Immunology
Marcus James Robinson, Isaak Quast, David Mathew Tarlinton
Summary: B cells reprogram complement to enhance germinal center responses. However, when B cell C3 activity is restricted, germinal centers collapse leading to impaired outputs.
Article
Multidisciplinary Sciences
Yunshun Chen, Bhupinder Pal, Geoffrey J. Lindeman, Jane E. Visvader, Gordon K. Smyth
Summary: This article extends our understanding of the development mechanism of breast cancer by providing quality control thresholds, processed data objects, complete cell annotation, and R code for analysis of a large-scale single-cell RNA expression atlas.
Article
Biochemistry & Molecular Biology
Alexandra R. Dvorscek, Craig McKenzie, Marcus J. Robinson, Zhoujie Ding, Catherine Pitt, Kristy O'Donnell, Dimitra Zotos, Robert Brink, David M. Tarlinton, Isaak Quast
Summary: IL-21 acts as a key regulator in the initial B cell response, accelerating cell cycle progression and fueling cyclic re-entry of B cells, thereby promoting plasma cell differentiation.
Article
Cell Biology
Johannes Wichmann, Catherine Pitt, Samantha Eccles, Alexandra L. Garnham, Connie S. N. Li-Wai-Suen, Rose May, Elizabeth Allan, Stephen Wilcox, Marco J. Herold, Gordon K. Smyth, Brendon J. Monahan, Tim Thomas, Anne K. Voss
Summary: Histone acetylation is crucial for chromatin conformation and gene transcription, and TIP60 is a key enzyme involved in this process. Loss of TIP60 leads to cell growth arrest and abnormal chromosome alignment during mitosis. However, cell survival is not affected. TIP60 is essential for the acetylation of H2AZ at lysine 7 and plays a role in the activation of transcription for thousands of genes, including those involved in metabolism.
CELL DEATH & DISEASE
(2022)
Editorial Material
Immunology
Isaak Quast, David Tarlinton
Summary: A new study reveals a novel protein immunization strategy that enhances the durability of germinal centers and improves immunological outcomes by delivering the protein slowly over a 12-day period.
Article
Multidisciplinary Sciences
Wing Fuk Chan, Hannah D. Coughlan, Yunshun Chen, Christine R. Keenan, Gordon K. Smyth, Andrew C. Perkins, Timothy M. Johanson, Rhys S. Allan
Summary: By coupling the catalytic domain of DNA demethylating enzyme TET1 with transcriptional activators (TETact), the authors have developed an improved activation system that can induce transcription of stably silenced genes. The TETact system is applicable in various cell types and has the ability to reactivate embryonic haemoglobin genes in non-erythroid cells. It is expected that TETact will have significant implications in functional studies, genetic screens, and potential therapeutics.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Adam K. Wade-Vallance, Zhiyong Yang, Jeremy B. Libang, Marcus J. Robinson, David M. Tarlinton, Christopher D. C. Allen
Summary: Wade-Vallance et al. demonstrate that the binding of antigen or antibody to the B cell receptor triggers apoptosis in IgE plasma cells. This mechanism is relevant to allergic disease and its treatment through endogenous IgE regulation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Hesham D. D. Abdulla, Raed Alserihi, Christoffer Flensburg, Waruni Abeysekera, Meng-Xiao Luo, Daniel H. D. Gray, Xiaodong Liu, Gordon K. K. Smyth, Warren S. S. Alexander, Ian J. J. Majewski, Matthew P. P. McCormack
Summary: Abdulla et al. demonstrate that the LMO2 transcription factor promotes the development of T-lymphoblastic leukemia by inhibiting thymocyte competition in a transgenic mouse model.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Editorial Material
Immunology
Zhoujie Ding, David Tarlinton
Summary: BALT, formed in the lung during infancy and declining over childhood, plays a role in localized immune reactions against airway infections, including the production of germinal center-like B cells specific for respiratory pathogens.
Article
Biochemical Research Methods
Mengbo Li, Gordon K. Smyth
Summary: Mass spectrometry proteomics in biomedical research suffers from the problem of missing values in peptides. Many analysis strategies have been proposed to distinguish different types of missing values and estimate detection probabilities. A logit-linear function is used to accurately model the detection probability, showing that missing values are related to peptide intensity. A probability model is developed to infer the distribution of unobserved intensities from observed values.
Article
Biochemistry & Molecular Biology
Pedro L. Baldoni, Yunshun Chen, Soroor Hediyeh-zadeh, Yang Liao, Xueyi Dong, Matthew E. Ritchie, Wei Shi, Gordon K. Smyth
Summary: Differential expression analysis of RNA-seq is commonly used in bioinformatics. However, transcript-level quantifications are more uncertain due to the ambiguity of sequence reads. To address this issue, a new method is proposed to estimate the overdispersion caused by read-to-transcript ambiguity and generate scaled transcript counts, which improves the efficiency and accuracy of differential analysis.
NUCLEIC ACIDS RESEARCH
(2023)