Article
Immunology
David Gomez Jimenez, Can Altunbulakli, Sabine Swoboda, Aastha Sobti, David Askmyr, Ashfaq Ali, Lennart Greiff, Malin Lindstedt
Summary: The incidence of HPV+ tonsillar cancer has increased significantly in recent decades. This study used single-cell RNA-sequencing to investigate the myeloid compartment in HPV+ tonsillar cancer. The researchers observed an expansion of the myeloid compartment and interferon-induced cellular responses in dendritic cells and monocyte-macrophages. They discovered four dendritic cell lineages, two macrophage polarization processes, and identified biomarkers that correlate with patient survival. This study contributes to understanding the role of myeloid cells in HPV-driven tonsillar cancer and provides potential prognostic markers.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Jintao Gu, Nan Mu, Bo Jia, Qingdong Guo, Luxiang Pan, Maorong Zhu, Wangqian Zhang, Kuo Zhang, Weina Li, Meng Li, Lichun Wei, Xiaochang Xue, Yingqi Zhang, Wei Zhang
Summary: This study presents a novel preclinical model for radiobiological studies and identifies a radiation-tolerant persister subpopulation that drives radioresistance by activating DNA damage repair and promoting stemness. The NF-kappa B-YY1-miR-103a regulatory axis is essential for the function of the radiation-tolerant persister cells. Furthermore, transferrin-functionalized nanoparticles improve radiosensitivity and provide a significant survival benefit.
Article
Biology
Marina Ainciburu, Teresa Ezponda, Nerea Berastegui, Ana Alfonso-Pierola, Amaia Vilas-Zornoza, Patxi San Martin-Uriz, Diego Alignani, Jose Lamo-Espinosa, Mikel San-Julian, Tamara Jimenez-Solas, Felix Lopez, Sandra Muntion, Fermin Sanchez-Guijo, Antonieta Molero, Julia Montoro, Guillermo Serrano, Aintzane Diaz-Mazkiaran, Miren Lasaga, David Gomez-Cabrero, Maria Diez-Campelo, David Valcarcel, Mikel Hernaez, Juan P. Romero, Felipe Prosper
Summary: In this study, single-cell RNA sequencing was used to analyze hematopoietic stem and progenitor cells in young and elderly healthy individuals. The study found changes in the composition and regulation of these cells during aging and myeloid malignant transformation. By analyzing gene expression dynamics and constructing gene regulatory networks, the study also identified specific alterations in transcription factors and regulatory mechanisms associated with myeloid malignancies. This research demonstrates the potential of single-cell technologies combined with computational analysis tools for studying complex biological systems and developing personalized therapeutic approaches.
Article
Biochemistry & Molecular Biology
Yanan Zhai, Prashant Singh, Anna Dolnik, Peter Brazda, Nader Atlasy, Nunzio del Gaudio, Konstanze Dohner, Hartmut Dohner, Saverio Minucci, Joost Martens, Lucia Altucci, Wout Megchelenbrink, Lars Bullinger, Hendrik G. Stunnenberg
Summary: This study explored the clonal heterogeneity of diagnosis and relapse pairs in acute myeloid leukemia patients at genetic and transcriptional levels, revealing the underlying pathways and genes contributing to cancer recurrence. Single cell RNA data showed extensive expression differences between patients and diagnosis-relapse pairs, indicating potential mechanisms leading to therapeutic resistance and AML recurrence.
Article
Cell & Tissue Engineering
Yi-Dan Liu, Ying-Ting Zhu, Yun-Hong Shi, Xiu-Xing Liu, Wen-Ru Su, Ye-Hong Zhuo
Summary: Adult neural stem cells (NSCs) are confined to specific regions of the mammalian brain and possess the ability to self-renew and differentiate into various cell lineages. Single-cell RNA sequencing technology has provided detailed insights into the heterogeneity of NSCs and their transcriptional changes in aging and brain tumors. Understanding NSCs in both physiological and pathological contexts is crucial for rejuvenating the aging brain and restoring normal brain function in neurological disorders.
STEM CELLS AND DEVELOPMENT
(2023)
Article
Oncology
Zheng Wang, Chengyan Chai, Rui Wang, Yimei Feng, Lei Huang, Yiming Zhang, Xia Xiao, Shijie Yang, Yunfang Zhang, Xi Zhang
Summary: This study utilized advanced single-cell RNA sequencing to construct a comprehensive atlas of over 130,000 single-MSC transcriptomes across multiple tissues and donors, revealing seven tissue-specific and five conserved MSC subpopulations with distinct gene expression signatures. The study demonstrated the significant contribution of extracellular matrix to MSC heterogeneity and identified potential improvements in MSC-based therapeutic efficacy.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Biology
Zhi Dong, Lan Pang, Zhiguo Liu, Yifeng Sheng, Xiaoping Li, Xavier Thibault, Amy Reilein, Daniel Kalderon, Jianhua Huang
Summary: This study used single-cell RNA sequencing to investigate the gene expression patterns of Drosophila ovarian follicle stem cells (FSCs) and their derivatives. The results revealed spatial heterogeneity and dynamic changes in phenotype. The findings provide a valuable resource and foundation for understanding stem cell behavior and disease development.
Article
Oncology
Aram S. Modrek, Eskil Eskilsson, Ravesanker Ezhilarasan, Qianghu Wang, Lindsey D. Goodman, Yingwen Ding, Ze-Yan Zhang, Krishna P. L. Bhat, Thanh-Thuy T. Le, Floris P. Barthel, Ming Tang, Jie Yang, Lihong Long, Joy Gumin, Frederick F. Lang, Roel G. W. Verhaak, Kenneth D. Aldape, Erik P. Sulman
Summary: This study demonstrates that PDPN expression is associated with prognosis and treatment resistance in gliomas. Knockdown of PDPN sensitizes glioma cells to radiation therapy and improves overall survival in a mouse model. Therefore, PDPN may serve as a novel therapeutic target for gliomas.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Xiao-Huan Liu, Jin-Ting Zhou, Chun-xia Yan, Cheng Cheng, Jing-Na Fan, Jing Xu, Qiangsun Zheng, Qiang Bai, Zongfang Li, Shengbin Li, Xiaoming Li
Summary: The deficiency of ApoA4 leads to the reprogramming of liver immune cells and promotes the increase of specific subsets, exacerbating hepatic inflammation in NAFLD. These findings may provide new therapeutic targets for the treatment of NAFLD.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jennifer K. Matsui, Haley K. Perlow, Alex R. Ritter, Rituraj Upadhyay, Raju R. Raval, Evan M. Thomas, Sasha J. Beyer, Clement Pillainayagam, Justin Goranovich, Shirley Ong, Pierre Giglio, Joshua D. Palmer
Summary: This review discusses the treatment modalities for glioblastoma, the mechanisms of radioresistance, and promising radiosensitizers. Small molecules and immunotherapy agents used in conjunction with radiotherapy have been studied in clinical trials. Recent preclinical studies regarding radiosensitizers for glioblastoma are also discussed.
Article
Oncology
Zhuang Sun, Xiaohui Wang, Jingyun Wang, Jing Wang, Xiao Liu, Runda Huang, Chunyan Chen, Meiling Deng, Hanyu Wang, Fei Han
Summary: This study identified 1182 differentially expressed genes between radioresistant and radiosensitive NPC tissue samples, with 22 genes upregulated and 1160 genes downregulated in the radioresistant group. Integration analysis revealed 10 major NPC radiation resistance network models, with three core genes DOCK4, MCM9, and POPDC3 identified among 12 common downregulated genes. Further experimental studies on these core genes are warranted to deepen the understanding of NPC radioresistance mechanisms.
Article
Genetics & Heredity
Chen Zhang, Xueshuai Han, Jingkun Liu, Lei Chen, Ying Lei, Kunying Chen, Jia Si, Tian-yi Wang, Hui Zhou, Xiaoyun Zhao, Xiaohui Zhang, Yihua An, Yueying Li, Qian-Fei Wang
Summary: By single-cell RNA sequencing, this study identified five distinct subpopulations of ex vivo-expanded mesenchymal stem cells (MSCs). Among them, a stem-like subpopulation exhibited strong proliferation and stemness signatures, while another subpopulation of prechondrocytes played a role in immunoregulation. These findings contribute to a better understanding and application of MSCs.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2022)
Article
Oncology
Lily Nguyen, Sophie Dobiasch, Gunter Schneider, Roland M. Schmid, Omid Azimzadeh, Kristiyan Kanev, Dominik Buschmann, Michael W. Pfaffl, Stefan Bartzsch, Thomas E. Schmid, Daniela Schilling, Stephanie E. Combs
Summary: The study aimed to elucidate the mechanisms of radioresistance in pancreatic cancer cells, revealing that increased cell viability and reduced oxidative stress may contribute to the development of radioresistance.
RADIOTHERAPY AND ONCOLOGY
(2021)
Article
Environmental Sciences
Guiya Xiong, Bing Zhang, Bo Song, Huan Luo, Lina Zhao, Zhibin Wang, Zhijun Zhou, Xiuli Chang
Summary: The study investigated the neurotoxicity of Paraquat by analyzing its impact on murine neural stem cell differentiation using single-cell RNA sequencing. The results showed that Paraquat exposure changed the proportions of different cell subtypes, leading to reduced neurons and increased astrocytes, with mechanisms involving increased intracellular and mitochondrial reactive oxygen species. Additionally, Paraquat dysregulated cell-to-cell communications and pretreatment with the antioxidant MitoTEMPO ameliorated the neuronal reduction caused by Paraquat.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Immunology
Yunhu Yu, Fang Cao, Yanquan Xiong, Hang Zhou
Summary: This study revealed that SP1 interacts with NLRP6 inflammasome to enhance malignant behaviors, immune evasion and radioresistance in glioma cells. Downregulation of SP1 or upregulation of NLRP6 can decrease malignancy of cells, but also affect immune activity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Letter
Hematology
Rohan Kodgule, Jie Chen, Pooja Khonde, Joshua Robinson, Amy D'Albora, Lisa Cook, Catrina C. Fronick, Robert Fulton, Sridhar Nonavinkere Srivatsan, Patrick J. Cimino, Eric J. Duncavage
Review
Pathology
Rebecca A. Yoda, Patrick J. Cimino
Summary: Hemangioblastoma is a vascular tumor of the central nervous system associated with loss of function of the VHL gene. It primarily occurs in the cerebellum, brainstem, and spinal cord, leading to significant morbidity and mortality in affected patients. Accurate diagnosis is crucial for surgical neuropathology, as other VHL-associated tumors may mimic its histology.
JOURNAL OF PATHOLOGY AND TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
James H. Park, Abdullah H. Feroze, Samuel N. Emerson, Anca B. Mihalas, C. Dirk Keene, Patrick J. Cimino, Adrian Lopez Garcia de Lomana, Kavya Kannan, Wei-Ju Wu, Serdar Turkarslan, Nitin S. Baliga, Anoop P. Patel
Summary: In this study, the authors modeled the tumor evolutionary trajectories during standard-of-care treatment for glioblastoma using multi-omic single-cell analysis. They identified a network of regulators that mediate treatment-induced shifts in tumor cell states and developed consensus networks that modulate cell state transitions across primary and recurrent tumor cells. By matching targeted therapies to active regulatory networks, they proposed a framework for applying single-cell-based precision medicine approaches to individual patients in different treatment settings.
NPJ PRECISION ONCOLOGY
(2022)
Article
Clinical Neurology
Patrick J. Cimino, Courtney Ketchum, Rust Turakulov, Omkar Singh, Zied Abdullaev, Caterina Giannini, Peter Pytel, Giselle Yvette Lopez, Howard Colman, MacLean P. Nasrallah, Mariarita Santi, Igor Lima Fernandes, Jeff Nirschl, Sonika Dahiya, Stewart Neill, David Solomon, Eilis Perez, David Capper, Haresh Mani, Dario Caccamo, Matthew Ball, Michael Badruddoja, Rati Chkheidze, Sandra Camelo-Piragua, Joseph Fullmer, Sanda Alexandrescu, Gabrielle Yeaney, Charles Eberhart, Maria Martinez-Lage, Jie Chen, Leor Zach, B. K. Kleinschmidt-DeMasters, Marco Hefti, Maria-Beatriz Lopes, Nicholas Nuechterlein, Craig Horbinski, Fausto J. Rodriguez, Martha Quezado, Drew Pratt, Kenneth Aldape
Summary: This study provides further evaluation and classification of high-grade astrocytoma with piloid features (HGAP). The study identifies three distinct subtypes of HGAP and discovers characteristic genetic mutations and epigenetic changes. This research is important for understanding the pathogenesis and clinical characteristics of HGAP.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Zhichao Wu, Sharika Rajan, Hye-Jung Chung, Mark Raffeld, Pavalan Panneer Selvam, Leonille Schweizer, Arie Perry, David Samuel, Caterina Giannini, Aditya Ragunathan, Matthew P. Frosch, Michael S. Marshall, Daniel R. Boue, Kliment Donev, Stewart G. Neill, Igor Fernandes, Adam Resnick, Brian Rood, Thomas J. Cummings, Anne F. Buckley, Linda Szymanski, Osorio Lopes Abath Neto, Leor Zach, Howard Colman, Samuel Cheshier, Jennifer Ziskin, Manoj Tyagi, David Capper, Zied Abdullaev, Patrick J. Cimino, Martha Quezado, Drew Pratt, Kenneth Aldape
ACTA NEUROPATHOLOGICA
(2022)
Article
Multidisciplinary Sciences
Siobhan S. Pattwell, Sonali Arora, Nicholas Nuechterlein, Michael Zager, Keith R. Loeb, Patrick J. Cimino, Nikolas C. Holland, Noemi Reche-Ley, Hamid Bolouri, Damian A. Almiron Bonnin, Frank Szulzewsky, Vaishnavi V. Phadnis, Tatsuya Ozawa, Michael J. Wagner, Michael C. Haffner, Junyue Cao, Jay Shendure, Eric C. Holland
Summary: This article highlights the previously unidentified role of the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis. TrkB.T1 is an important isoform in these processes and is expressed in both embryonic and adult tumors. The study also reveals its interaction with developmental and oncogenic signaling pathways, suggesting its potential to reshape our understanding of developmental systems and oncology.
Article
Oncology
Yang Liu, Fu-Ju Chou, Fengchao Lang, Meili Zhang, Hua Song, Wei Zhang, Dionne L. Davis, Nicole J. Briceno, Yang Zhang, Patrick J. Cimino, Kareem A. Zaghloul, Mark R. Gilbert, Terri S. Armstrong, Chunzhang Yang
Summary: This study reveals that mutations of the IDH gene are common in human malignancies and play critical roles in malignant transformation. The PI3K/AKT signaling pathway is enhanced in IDH-mutated cancer cells. Combining the AKT inhibitor Ipa with the genotoxic agent TMZ shows synergistic therapeutic effect in IDH-mutated cancer cells.
CLINICAL CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Zhihong Chen, Nishant Soni, Gonzalo Pinero, Bruno Giotti, Devon J. Eddins, Katherine E. Lindblad, James L. Ross, Montserrat Puigdelloses Vallcorba, Tanvi Joshi, Angelo Angione, Wes Thomason, Aislinn Keane, Nadejda M. Tsankova, David H. Gutmann, Sergio A. Lira, Amaia Lujambio, Eliver E. B. Ghosn, Alexander M. Tsankov, Dolores Hambardzumyan
Summary: Myeloid cells are the majority of immune cells in tumors and play a critical role in tumor growth and resistance to therapy. By using CRISPR/Cas9-based genome editing, researchers have created a mouse model lacking all monocyte chemoattractant proteins. They found that blocking monocyte infiltration leads to compensatory neutrophil influx, highlighting the importance of targeting both cell types simultaneously for improved cancer treatments.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Antonio De Falco, Francesca Caruso, Xiao-Dong Su, Antonio Iavarone, Michele Ceccarelli
Summary: The authors develop SCEVAN, a variational algorithm for copy number-based clonal structure inference in single-cell RNA-seq data, which can characterize the evolution and heterogeneity in tumors and the microenvironment. SCEVAN can automatically and accurately discriminate between malignant and non-malignant cells, resulting in a practical framework to analyze tumors and their microenvironment.
NATURE COMMUNICATIONS
(2023)
Letter
Clinical Neurology
Allison Shelbourn, Nicholas Nuechterlein, Carolina Angelica Parada, Jessica Eaton, Mallory Tucker, Manuel Ferreira Jr, Patrick J. Cimino
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Letter
Clinical Neurology
Nicholas Nuechterlein, Allison Shelbourn, Patrick J. Cimino
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Cell Biology
Frank Szulzewsky, Sonali Arora, Aleena K. S. Arakaki, Philipp Sievers, Damian A. Almiron Bonnin, Patrick J. Paddison, Felix Sahm, Patrick J. Cimino, Taranjit S. Gujral, Eric C. Holland
Summary: The study investigates the role of YAP1-MAML2 gene fusion in the formation of meningioma and demonstrates that YAP1-MAML2 is a causal oncogenic driver in meningioma.
GENES & DEVELOPMENT
(2022)
Article
Oncology
Jinxiang Dai, Patrick J. Cimino, Kenneth H. I. I. I. I. I. I. Gouin, Candice A. Grzelak, Alexander Barrett, Andrea R. Lim, Annalyssa Long, Stephanie Weaver, Lindsey T. Saldin, Aiyedun Uzamere, Vera Schulte, Nigel Clegg, Laura Pisarsky, David Lyden, Mina J. Bissell, Simon Knott, Alana L. Welm, Jason H. Bielas, Kirk C. Hansen, Frank Winkler, Eric C. Holland, Cyrus M. Ghajar
Summary: This study reveals that escape from the single-cell or micrometastatic state is the rate-limiting step towards brain metastasis, with laminin-211 deposited by astrocytes playing a key role in inducing DTC dormancy.
