Article
Cell Biology
Weihong Gu, Darling Melany C. Madrid, Sebastian Joyce, John P. Driver
Summary: In this study, single-cell RNA sequencing was used to create a cell atlas of the early-adolescent pig thymus, revealing conserved features and species-specific differences compared to human thymocytes. The study also identified unconventional T cell types with gene expression profiles associated with innate effector functions and characterized the functional diversity of pig iNKT cells. These findings provide important insights into pig T cell development.
Article
Immunology
Thomas Hagglof, Raksha Parthasarathy, Nathaniel Liendo, Elizabeth A. Dudley, Elizabeth A. Leadbetter
Summary: Receptor Interacting Protein Kinase 1 (RIPK1) and caspase-8 (Casp8) play important roles in apoptosis and autoinflammatory diseases. RIPK1 is involved in the differentiation and homeostasis of T cells. RIPK1 also regulates NK1.1 expression and iNKT cell development, and both Casp8 and RIPK1 mediate iNKT cytokine effector responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Masashi Watanabe, Sofia Celli, Farrah A. Alkhaleel, Richard J. Hodes
Summary: This study elucidates the mechanism by which antigen-presenting T cells acquire B7 molecules via CD28-dependent trogocytosis from other cells and provide critical B7 co-stimulation to developing iNKT cells in thymic T cell development.
Article
Cell Biology
Jie Wang, Indra Adrianto, Kalpana Subedi, Tingting Liu, Xiaojun Wu, Qijun Yi, Ian Loveless, Congcong Yin, Indrani Datta, Derek B. B. Sant'Angelo, Mitchell Kronenberg, Li Zhou, Qing-Sheng Mi
Summary: Unlike conventional alpha beta T cells, invariant natural killer T (iNKT) cells undergo differentiation to become functional iNKT1/2/17 cells in the thymus. This study used single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to profile the transcriptomes and chromatin accessibility states of iNKT cells, uncovering distinct developmental programs and cellular heterogeneity. It identified a novel transcription factor, Cbf beta, as a key regulator for early iNKT cell commitment and differentiation.
Article
Health Care Sciences & Services
Wendao Liu, Noam Shomron
Summary: MicroRNAs regulate gene expression by binding to mRNAs, reducing target gene expression levels and noise. Single-cell RNA sequencing technology has been used to study miRNA and mRNA expression in single cells. However, technical noise from scRNA-seq can mask the effect of miRNAs on gene expression noise. Improvements in experimental design and computational analysis are necessary to reduce technical noise.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Immunology
Thomas Baranek, Carolina de Amat Herbozo, Thierry Mallevaey, Christophe Paget
Summary: Invariant natural killer T (iNKT) cells are important biomarkers and targets for immunotherapy. Recent studies have revealed the heterogeneity of iNKT cells and challenged our understanding of their development and differentiation. A new model is proposed to explain the classification and differentiation of iNKT cells.
TRENDS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Jie Wang, Kai Li, Xilin Zhang, Guihua Li, Tingting Liu, Xiaojun Wu, Stephen L. Brown, Li Zhou, Qing-Sheng Mi
Summary: MiR-155 plays a key role in regulating the development of iNKT cells, with its expression gradually downregulated during development. It modulates multiple targets and signaling pathways, fine-tuning iNKT cell development and influencing the balance between iNKT1 and iNKT2 differentiation. MiR-155 serves as an epigenetic regulator, coordinating various pathways to precisely regulate iNKT cell development and functional differentiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Liang Cao, Eva Morgun, Samantha Genardi, Lavanya Visvabharathy, Yongyong Cui, Haochu Huang, Chyung-Ru Wang
Summary: The study reveals the critical role of METTL14-dependent m(6)A modification in iNKT cell development and function. Loss of METTL14-dependent m(6)A modification leads to reduced numbers and impaired maturation of iNKT cells, as well as decreased responsiveness to stimulation.
Article
Biology
Lydia K. Lutes, Zoe Steier, Laura L. McIntyre, Shraddha Pandey, James Kaminski, Ashley R. Hoover, Silvia Ariotti, Aaron Streets, Nir Yosef, Ellen A. Robey
Summary: Thymocytes with low self-reactivity experience shorter TCR signals during positive selection and complete the process more slowly compared to those with high self-reactivity. Additionally, cells with low self-reactivity retain a preselection gene expression signature, including genes related to modulating TCR sensitivity and a novel group of ion channel genes, as they mature. These findings suggest that thymocytes with low self-reactivity downregulate TCR sensitivity more slowly during positive selection and that membrane ion channel expression is associated with thymocyte self-reactivity and progression through positive selection.
Article
Immunology
Claudia Haftmann, Pascale Zwicky, Florian Ingelfinger, Florian Mair, Stefan Floess, Rene Riedel, Pawel Durek, Marianne R. Spalinger, Ekaterina Friebel, Brian P. Leung, Mirjam Lutz, Nicole Puertas, Ana Amorim, Stefanie Scharli, Benedict Becher, Jan Kisielow, Ari Waisman, Mir-Farzin Mashreghi, Jochen Huehn, Burkhard Becher
Summary: Medullary thymic epithelial cells (mTECs) play a crucial role in regulating T cell immune tolerance by negatively selecting self-reactive T cells and promoting the development of regulatory T cells. Dysfunctional regulatory T cells may be a key factor in the development of autoimmune diseases.
SCIENCE IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Thomas Barthlott, Adam E. Handel, Hong Ying Teh, Rushika C. Wirasinha, Katrin Hafen, Saulius Zuklys, Benoit Roch, Stuart H. Orkin, Jean-Pierre de Villartay, Stephen R. Daley, Georg A. Hollaender
Summary: Thymic T cell development and T cell receptor repertoire selection rely on molecular signals from thymic epithelial cells (TEC), whose development and function are epigenetically regulated. Disruption of PRC2 activity alters H3K27me3 configuration, impairs TEC functions, and affects T cell development.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Laura B. Chopp, Xiaoliang Zhu, Yayi Gao, Jia Nie, Jatinder Singh, Parimal Kumar, Kelly Z. Young, Shil Patel, Caiyi Li, Mariah Balmaceno-Criss, Melanie S. Vacchio, Michael M. Wang, Ferenc Livak, Juanita L. Merchant, Lie Wang, Michael C. Kelly, Jinfang Zhu, Remy Bosselut
Summary: The transcription factors Zfp281 and Zfp148 play important roles in initiating CD4(+) lineage gene expression and regulating cytokine expression by T(H)2 effector cells. They promote the differentiation of CD4(+) T cells in the thymus and enhance T(H)2 cytokine expression in peripheral T cells, but do not affect the expression of the T(H)2 lineage-determining transcription factor Gata3.
SCIENCE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Meriam Nefla, Nicola J. Darling, Manuel van Gijsel Bonnello, Philip Cohen, J. Simon C. Arthur
Summary: Salt Inducible Kinases 2 (SIK2) and 3 (SIK3) play important roles in thymic T cell development, with their loss leading to decreased numbers of peripheral T cells and defects in negative and/or positive selection in the thymus.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Qian Zhang, Jiayu Zhang, Tong Lei, Zhanfeng Liang, Xue Dong, Liguang Sun, Yong Zhao
Summary: Thymic epithelial cells (TECs) are crucial for the generation of self-tolerant T cells, and the epigenetic regulation mediated by Sirt6 may play a key role in the development of thymic tuft cells.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Victor Olariu, Mary A. Yui, Pawel Krupinski, Wen Zhou, Julia Deichmann, Emil Andersson, Ellen Rothenberg, Carsten Peterson
Summary: This study presents a three-level dynamic model to explain the commitment dynamics of thymic cell development, including a core gene regulatory network architecture, stochastically controlled chromatin-state gate, and single-cell proliferation model.
Article
Multidisciplinary Sciences
Giulia Nato, Alessandro Corti, Elena Parmigiani, Elena Jachetti, Daniele Lecis, Mario Paolo Colombo, Domenico Delia, Annalisa Buffo, Lorenzo Magrassi
Summary: Xenotransplantation of human neural precursor cells into the brains of mice and rats showed longer survival and differentiation only in NOD-SCID mice. Mixing the cells with partially differentiated cells or cellular extract from adult rat cerebellum extended the survival time of the xenograft.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Francesca Lovat, Pierluigi Gasparini, Giovanni Nigita, Karilyn Larkin, John C. Byrd, Mark D. Minden, Michael Andreeff, Bing Z. Carter, Carlo M. Croce
Summary: The study found that the loss of both miR-15/16 clusters may act as a potential oncogenic driver in the transition from chronic phase to blast crisis in CML patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Sabina Sangaletti, Roberto Ferrara, Claudio Tripodo, Marina Chiara Garassino, Mario Paolo Colombo
Summary: The lung serves as a site for both departure and arrival of metastases from primary lung tumors and extra-pulmonary origins, with myeloid cells, particularly neutrophils, playing a supportive role in this tissue microenvironment. In addition to neutrophils, other myeloid cell populations such as macrophages, dendritic cells, mast cells, basophils, and eosinophils contribute to the complexity of the lung cancer tumor microenvironment.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Editorial Material
Genetics & Heredity
Gerd A. Blobel, Douglas R. Higgs, Jennifer A. Mitchell, Dimple Notani, Richard A. Young
Summary: In this Viewpoint, five experts discuss our biological understanding of super-enhancers, how we can responsibly study their functions, and their opinions on whether names for enhancer clusters are an informative reflection of their functional properties.
NATURE REVIEWS GENETICS
(2021)
Letter
Multidisciplinary Sciences
Liguo Zhang, Alexsia Richards, M. Inmaculada Barrasa, Stephen H. Hughes, Richard A. Young, Rudolf Jaenisch
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Simone Camelliti, Valentino Le Noci, Francesca Bianchi, Chiara Storti, Francesca Arnaboldi, Alessandra Cataldo, Serena Indino, Elena Jachetti, Mariangela Figini, Mario Paolo Colombo, Andrea Balsari, Nicoletta Gagliano, Elda Tagliabue, Lucia Sfondrini, Michele Sommariva
Summary: TLR9-stimulated macrophages interacting with the Fc domain of anti-PD-1 antibody acquire an immunoregulatory phenotype, leading to dampening of CpG-ODN antitumor effect. This may represent another possible mechanism of anti-PD-1 antibody therapy resistance.
Article
Oncology
Maria Rosaria Sapienza, Giuseppe Benvenuto, Manuela Ferracin, Saveria Mazzara, Fabio Fuligni, Claudio Tripodo, Beatrice Belmonte, Daniele Fanoni, Federica Melle, Giovanna Motta, Valentina Tabanelli, Jessica Consiglio, Vincenzo Mazzara, Marcello Del Corvo, Stefano Fiori, Alessandro Pileri, Gaetano Ivan Dellino, Lorenzo Cerroni, Fabio Facchetti, Emilio Berti, Elena Sabattini, Marco Paulli, Carlo Maria Croce, Stefano A. Pileri
Summary: This study described neuronal features in blastic plasmacytoid dendritic cell neoplasm (BPDCN) for the first time, potentially changing our understanding of the disease and leading to new strategies for treatment. The identified neural metastatic inducers in BPDCN may offer therapeutic approaches for patients. The upregulation of neural genes in BPDCN is currently being investigated as therapeutic targets.
Review
Oncology
Maria Teresa Majorini, Mario Paolo Colombo, Daniele Lecis
Summary: This article reviews the role of mast cells in cancer, with a particular focus on breast cancer. Mast cells have an impact on the features and aggressiveness of cancer cells, but the eventual effect of mast cell infiltration is still controversial.
Article
Multidisciplinary Sciences
Felice Pepe, Laura Z. Rassenti, Yuri Pekarsky, Jadwiga Labanowska, Tatsuya Nakamura, Giovanni Nigita, Thomas J. Kipps, Veronica Balatti, Carlo M. Croce
Summary: Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by chromosomal aberrations. This study found that some CLL patients have undetected microdeletions, which are closely associated with chromosomal alterations in cancer. These findings may have clinical relevance for successful stratification of patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Maria Bellenghi, Giovanna Talarico, Laura Botti, Rossella Puglisi, Claudio Tabolacci, Paola Portararo, Annamaria Piva, Giada Pontecorvi, Alessandra Care, Mario P. Colombo, Gianfranco Mattia, Sabina Sangaletti
Summary: Dysregulated fatty acid metabolism interacts with oncogenic signals, worsening tumor aggressiveness. Overexpression of SCD5 gene reduces SPARC secretion, leading to decreased aggressiveness and reversal of Epithelial to Mesenchymal Transition (EMT) status in the metastatic clone of 4T1.
Biographical-Item
Oncology
Gary S. Stein, Carlo M. Croce
Article
Oncology
Riccardo Ray Colciago, Irene Fischetti, Carlotta Giandini, Eliana La Rocca, Tiziana T. Rancati, Alicia Rejas Mateo, Mario Paolo Colombo, Laura Lozza, Claudia Chiodoni, Elena Jachetti, Maria Carmen De Santis
Summary: Oncological treatments are rapidly changing with the introduction of targeted anticancer drugs and regimens, and radioimmunotherapy is emerging as a promising field. This review provides an overview of the synergistic use of radiotherapy and immunotherapy and addresses important questions about its implementation, the patient selection criteria, and when it becomes standard clinical practice.
EXPERT REVIEW OF ANTICANCER THERAPY
(2023)
Article
Oncology
Alessandro La Ferlita, Nipin Sp, Marina Goryunova, Giovanni Nigita, Raphael E. Pollock, Carlo M. Croce, Joal D. Beane
Summary: Soft-tissue sarcomas (STS), a rare and diverse group of tumors, have various subtypes characterized by differences in tumor biology and clinical outcomes. Small non-coding RNAs (sncRNAs), including miRNAs and tRNA-derived ncRNAs, play important roles in STS tumorigenesis and differentiation. However, the translation of these findings into clinical applications, such as biomarkers or therapeutic targets, remains challenging. This review summarizes the current understanding of sncRNAs in STS, with a focus on liposarcoma, and discusses their potential as novel biomarkers and therapeutic targets.
MOLECULAR CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Henry R. Kilgore, Peter G. Mikhael, Kalon J. Overholt, Ann Boija, Nancy M. Hannett, Catherine Van Dongen, Tong Ihn Lee, Young-Tae Chang, Regina Barzilay, Richard A. Young
Summary: This research reveals that different types of intracellular condensates have distinct chemical environments that affect molecular distribution. Machine learning approaches can predict the selective partitioning of molecules in condensates, providing insights for the development of small molecule therapeutics with optimal subcellular distribution and therapeutic benefits.
NATURE CHEMICAL BIOLOGY
(2023)
Meeting Abstract
Oncology
Lucia Casadei, Patricia Sarchet, Luciano Cascione, Giovanni Nigita, Fernanda Costas Casal de Faria, Carlo Maria Croce, Valerie Grignol, Raphael E. Pollock