Article
Biochemical Research Methods
Jake A. Melby, Willem J. de Lange, Jianhua Zhang, David S. Roberts, Stanford D. Mitchell, Trisha Tucholski, Gina Kim, Andreas Kyrvasilis, Sean J. McIlwain, Timothy J. Kamp, J. Carter Ralphe, Ying Ge
Summary: The study established an integrated method that allows sequential assessment of functional properties and top-down proteomics from the same hiPSC-ECT construct, revealing a strong correlation between contractile parameters and phosphorylation levels of alpha-tropomyosin. This integrated approach enables a holistic analysis of hiPSC-ECTs for applications in disease modeling, cardiotoxicity, and drug discovery.
JOURNAL OF PROTEOME RESEARCH
(2021)
Review
Cell & Tissue Engineering
Jennifer L. Dashnau, Qiong Xue, Monica Nelson, Eric Law, Lan Cao, Derek Hei
Summary: Advances in cellular reprogramming and gene-editing have provided potential for ex vivo cell therapies based on genetically engineered iPSC-derived allogeneic cells. There are differences in the processes used for generating these therapies compared to primary cell-derived autologous and allogeneic therapies. Regulatory guidance needs to address considerations such as donor eligibility, starting materials, cell banking, and genetic stability.
Review
Oncology
Marion Cannac, Jovan Nikolic, Philippe Benaroch
Summary: Anticancer immunotherapies aim to stimulate immune responses against tumor cells by modifying immune cells. Tumor-associated macrophages, which have pro-tumor properties, are abundant in the microenvironment of solid tumors. Researchers are trying to engineer these macrophages to counteract their pro-tumor activities and enhance their anti-tumor functions.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Yuanke Li, Haoqi Zhang, Ruikun Wang, Yuan Wang, Ruonan Li, Mingsheng Zhu, Xiangyun Zhang, Zhen Zhao, Yajuan Wan, Jie Zhuang, Hongkai Zhang, Xinglu Huang
Summary: By genetically engineering antibody-anchored membranes, agonistic antibody-boosted tumor cell nanovaccines were developed to activate costimulatory pathways and improve immune responses against tumors.
ADVANCED MATERIALS
(2023)
Article
Pharmacology & Pharmacy
Ayesha Arefin, Melissa Mendoza, Keri Dame, M. Iveth Garcia, David G. Strauss, Alexandre J. S. Ribeiro
Summary: We investigated the properties of engineered heart tissues (EHTs) made with different tissue casting batches and lines of differentiated hPSC-cardiomyocytes. The contractile outputs of EHTs were measured using a video-optical assay and compared with monolayers of hPSC-cardiomyocytes cultured in two-dimensional cultures. The drug-induced contractile responses were similar between monolayers and EHTs, and showed a close relationship with calcium kinetics.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Bimal Gurung, Gary Tse, Wendy Keung, Ronald A. Li, Wing Tak Wong
Summary: The study shows that hypokalaemia has pro-arrhythmic effects on hvCAS, leading to changes in conduction velocity, repolarization, refractoriness, and calcium handling. This bioengineered platform provides a useful tool for investigating electrophysiological substrates and conducting arrhythmia screening.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Environmental
Timothy Hua, Sonia Kiran, Yan Li, Qing-Xiang Amy Sang
Summary: This study explores the adverse effects of polystyrene microplastics (PS-MPs) on the human brain, showing that their exposure can affect embryonic brain-like tissue development and gene expression.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Cell Biology
Sophie Domingues, Annabelle Darle, Yolande Masson, Manoubia Saidani, Emilie Lagoutte, Ana Bejanariu, Julien Coutier, Raif Eren Ayata, Marielle Bouschbacher, Marc Peschanski, Gilles Lemaitre, Christine Baldeschi
Summary: Chronic wounds are difficult to heal due to prolonged inflammation, and there is a need for novel cell and tissue-based therapies. This study proposes a method using pluripotent stem cells to produce substitutes and reconstruct skin using a plasma-based matrix, showing promising results.
Article
Cell Biology
Amanda Cooper, Adam Sidaway, Abishek Chandrashekar, Elizabeth Latta, Krishnendu Chakraborty, Jingyou Yu, Katherine McMahan, Victoria Giffin, Cordelia Manickam, Kyle Kroll, Matthew Mosher, R. Keith Reeves, Rihab Gam, Elisa Arthofer, Modassir Choudhry, Tom Henley, Dan H. Barouch
Summary: Despite the rapid clinical translation of COVID-19 vaccines, there is still an opportunity for vaccine technology innovation to address current limitations and future pandemics. Researchers have developed a universal vaccine cell (UVC) that mimics the natural immune response to viral infection. In animal models and vaccinated individuals, this cellular vaccine has shown the ability to induce robust neutralizing antibodies and provide protection against viral variants.
CELL REPORTS MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Mahdi Ahmadi, Monireh Mahmoodi, Maryam Shoaran, Fereshteh Nazari-Khanamiri, Jafar Rezaie
Summary: New therapeutic approaches are urgently needed for combating metastatic cancers, which cause over 8 million deaths per year worldwide. Mesenchymal stem cells (MSCs) have shown potential as a novel treatment option for cancer, with their exosomes playing a crucial role in regulating tumor progression. However, there is still controversy surrounding the exact association between MSC-derived exosomes and tumors. Nevertheless, the use of MSC-derived exosomes as drug delivery systems and standalone therapeutics is actively being explored, and engineering these exosomes to target tumor cells shows promise in improving the efficacy of antitumor therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Hua Huang, Yuwen Pan, Jiaming Huang, Chunyu Zhang, Yuandong Liao, Qiqiao Du, Shuhang Qin, Yili Chen, Hao Tan, Ming Chen, Manman Xu, Meng Xia, Yunyun Liu, Jie Li, Tianyu Liu, Qiaojian Zou, Yijia Zhou, Li Yuan, Wei Wang, Yanchun Liang, Chao yun Pan, Junxiu Liu, Shuzhong Yao
Summary: A patient-derived organoids (PDOs) biobank containing 67 cases of cervical cancer was established to accurately reproduce tumor characteristics. The in vitro co-culture of PDOs with tumor-infiltrating lymphocytes (TILs) demonstrated clear immune therapy responses. This study supports the potential of the PDOs platform in guiding treatment for cervical cancer.
Article
Engineering, Biomedical
Yun Chang, Gyuhyung Jin, Weichuan Luo, Qian Luo, Juhyung Jung, Sydney N. Hummel, Sandra Torregrosa-Allen, Bennett D. Elzey, Philip S. Low, Xiaojun Lance Lian, Xiaoping Bao
Summary: Adoptive CAR-engineered NK cells have potential for cancer treatment, but limited immunological memory and donor cell availability hinder their applications. We evaluated different CAR constructs to enhance NK cell proliferation and anti-tumor cytotoxicity. We genetically engineered hPSCs with optimized CARs and differentiated them into dual CAR-NK cells. The memory-like hPSC-NK cells showed enhanced anti-tumor activity through antigen-dependent activation of signaling pathways. Our modular hPSC CAR-NK engineering platform is a realistic strategy for off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy.
BIOACTIVE MATERIALS
(2023)
Review
Biochemistry & Molecular Biology
Daehwan Kim, Sangho Roh
Summary: Stem cell research is crucial for studying human diseases, genetic preservation, and improving animals. Efforts have been made to establish true ESCs in various species, although capturing true bESCs in cattle remains a challenge. This review discusses the difficulties in establishing bESCs with different culture conditions and introduces alternative induced pluripotent stem cells and extended pluripotent stem cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Shuyi Gu, Gaosong Wu, Dong Lu, Guofeng Meng, Yu Wang, Liming Tang, Weidong Zhang
Summary: Drug-induced nephrotoxicity is a common cause of acute kidney injury. Organoids derived from human-induced pluripotent stem cells have been shown to be a promising model for studying nephrotoxicity. This study demonstrated that Esculentoside A, a compound isolated from the root of Phytolacca acinose Roxb., can induce kidney injury in vivo and in kidney organoids. The findings suggest that kidney organoids can be used as a reliable platform for assessing nephrotoxicity caused by Chinese medicine.
PHYTOTHERAPY RESEARCH
(2023)
Review
Cell Biology
Rie Ouchi, Hiroyuki Koike
Summary: The discovery of human pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells (iPSCs), has greatly advanced our understanding of human developmental biology and has been used in drug discovery and disease treatments. PSC-derived organoids, which replicate the complex structures of living organs, have been created and used in various fields. iPSC-derived organoids, with their genetic background matching the donor, are useful for disease modeling, pathophysiology elucidation, and drug screening. They are also promising in regenerative medicine as a low-risk alternative to organ transplantation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Erik N. Bergstrom, Jens Luebeck, Mia Petljak, Azhar Khandekar, Mark Barnes, Tongwu Zhang, Christopher D. Steele, Nischalan Pillay, Maria Teresa Landi, Vineet Bafna, Paul S. Mischel, Reuben S. Harris, Ludmil B. Alexandrov
Summary: This study provides a comprehensive characterization of clustered mutations and small insertions and deletions in cancer genomes. The results show that clustered mutations are enriched in driver genes and associated with differential gene expression and overall survival. Different mutational processes contribute to clustered insertions and deletions, including specific signatures in tobacco smokers and homologous-recombination-deficient cancers. APOBEC3 plays a significant role in clustered substitutions, although only a small percentage matches APOBEC3 patterns. The study also reveals the associations between the activation-induced deaminase (AID) and APOBEC3 family of deaminases with kataegis (longer strand-coordinated events).
Article
Clinical Neurology
Julia M. T. Ledderose, Jorge A. Benitez, Amanda J. Roberts, Rachel Reed, Willem Bintig, Matthew E. Larkum, Robert N. S. Sachdev, Frank Furnari, Britta J. Eickholt
Summary: PTEN mutations are associated with autism spectrum disorders and regulate neuron size and connectivity in brain circuits involved in sensory processing. Knock-in mice with PTEN T366 substitution exhibit cognitive deficits and selective sensory impairments. Differences in connectivity to the primary somatosensory cortex are observed in Pten(T366A/T366A) brains.
Article
Immunology
Jad N. Kanbar, Shengyun Ma, Eleanor S. Kim, Nadia S. Kurd, Matthew S. Tsai, Tiffani Tysl, Christella E. Widjaja, Abigail E. Limary, Brian Yee, Zhaoren He, Yajing Hao, Xiang-Dong Fu, Gene W. Yeo, Wendy J. Huang, John T. Chang
Summary: The long noncoding RNA Malat1 affects the differentiation of effector and memory CD8(+) T cell subsets by repressing memory-associated genes through an interaction with Ezh2. This study expands our knowledge of the role of long noncoding RNAs in CD8(+) T cell biology.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Review
Cell Biology
Phuong Le, Noorsher Ahmed, Gene W. Yeo
Summary: This article reviews recent advances in RNA imaging, discusses their impact on the field of RNA biology, and explores current trends and potential. Le et al. provide a comprehensive overview of technologies for imaging RNAs in fixed and live cells and the biological insights gained from these technologies.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jonghun Park, Mehrdad Bakhtiari, Bernt Popp, Michael Wiesener, Vineet Bafna
Summary: In this study, a method called code-adVNTR was developed to detect motif count variation and small indels within VNTRs. The results showed that code-adVNTR outperformed GATK-HaplotypeCaller in calling small indels within large VNTRs and successfully characterized coding VNTRs in the 1000 genomes data.
Article
Biochemistry & Molecular Biology
Yuan Chun Ding, Aaron W. Adamson, Mehrdad Bakhtiari, Carmina Patrick, Jonghun Park, Yael Laitman, Jeffrey N. Weitzel, Vineet Bafna, Eitan Friedman, Susan L. Neuhausen
Summary: This study investigates the role of VNTRs as causal modifiers of breast cancer risk. The results suggest that VNTRs may explain a proportion of the unexplained genetic risk for breast cancer.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Kathryn H. Morelli, Aaron A. Smargon, Gene W. Yeo
Summary: Disruptions in RNA processing are crucial in the development of neurological diseases. This Perspective discusses recent advancements in RNA-targeting therapies, focusing on the progress, limitations, and opportunities of a new generation of therapies utilizing RNA binding proteins and other endogenous RNA regulatory macromolecules for the treatment of human neurological disorders.
Article
Oncology
Florina-Nicoleta Grigore, Serena Johanna Yang, Clark C. Chen, Tomoyuki Koga
Summary: Brain and other central nervous system tumors are the second most common types of cancers among children and adolescents in the United States. Despite progress in diagnosis and treatment, brain cancer remains the leading cause of death in the pediatric population. Preclinical models, such as genetically engineered mouse models and patient-derived xenografts, play a crucial role in improving therapeutic strategies and survival for these patients.
Article
Oncology
Yuki Shinya, Hirotaka Hasegawa, Masahiro Shin, Kosuke Kashiwabara, Mariko Kawashima, Shunya Hanakita, Tomoyuki Koga, Satoshi Koizumi, Atsuto Katano, Yuichi Suzuki, Nobuhito Saito
Summary: This study found that age significantly affects post-treatment hemorrhage and nidus obliteration rate in patients with brain arteriovenous malformations (BAVMs) treated with stereotactic radiosurgery. Younger patients are more likely to experience reduced cerebral hemorrhages and achieve earlier nidus obliteration compared to older patients.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Stefan G. Kathman, Seong Joo Koo, Garrett L. Lindsey, Hsuan-Lin Her, Steven M. Blue, Haoxin Li, Steffen Jaensch, Jarrett R. Remsberg, Kay Ahn, Gene W. Yeo, Brahma Ghosh, Benjamin F. Cravatt
Summary: Researchers have identified electrophilic small molecules that can rapidly and selectively decrease the expression of transcripts encoding the androgen receptor and its splice variants in prostate cancer cells. These compounds engage a specific site in the RNA-binding protein NONO, suppressing the expression of cancer-relevant genes and impairing cancer cell proliferation. The findings suggest that NONO can be targeted by covalent small molecules to suppress protumorigenic transcriptional networks.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Ramya Raviram, Anugraha Raman, Sebastian Preissl, Jiangfang Ning, Shaoping Wu, Tomoyuki Koga, Kai Zhang, Cameron W. Brennan, Chenxu Zhu, Jens Luebeck, Kinsey Van Deynze, Jee Yun Han, Xiaomeng Hou, Zhen Ye, Anna K. Mischel, Yang Eric Li, Rongxin Fang, Tomas Baback, Joshua Mugford, Claudia Z. Han, Christopher K. Glass, Cathy L. Barr, Paul S. Mischel, Vineet Bafna, Laure Escoubet, Bing Ren, Clark C. Chen
Summary: In 2021, glioblastoma, the most common form of adult brain cancer, was reclassified by the World Health Organization into two subtypes based on genetic characteristics. The study analyzed the chromatin accessibility and transcription profiles of clinical samples from both types of tumors, revealing intratumoral heterogeneity and shared chromatin structure among tumor cells. Silencing specific transcription factors suppressed tumor growth, suggesting a potential therapeutic target for addressing the challenges associated with intratumoral heterogeneity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Matteo P. D'Antonio, Jennifer P. D. Nguyen, Timothy D. Arthur, Hiroko A. Matsui, Agnieszka D'Antonio-Chronowska, Kelly A. Frazer
Summary: This study identifies 2,578 eQTLs associated with specific developmental stages, tissues, and cell types using spatiotemporal information of 966 RNA-seq cardiac samples. The colocalization between eQTLs and GWAS signals reveals the impact of genetic variants on cardiac traits and diseases. These findings shed light on the specific effects of cardiac GWAS variants on developmental stages, tissues, and cell types.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Jacqueline S. Gerritsen, Joseph S. Faraguna, Rudy Bonavia, Frank B. Furnari, Forest M. White
Summary: This study investigated the relationship between specific EGFR phosphorylation sites and the signaling network as well as cell response. The results showed that the EGFR network remains resilient even with multiple Y-to-F mutations in the C-terminal tail. Additionally, the study revealed previously unidentified network nodes associated with EGFR signaling. The data-driven model highlighted the signaling network nodes associated with distinct EGF-driven cell responses.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemical Research Methods
Eric Kofman, Brian Yee, Hugo C. Medina-Munoz, Gene W. Yeo
Summary: FLARE is a fast and flexible workflow that identifies significantly edited regions from RNA-seq data. The FLARE codebase is available at https://github.com/YeoLab/FLARE.
BMC BIOINFORMATICS
(2023)
Article
Cell Biology
Evan A. Boyle, Hsuan-Lin Her, Jasmine R. Mueller, Jack T. Naritomi, Grady G. Nguyen, Gene W. Yeo
Summary: Skipper, an end-to-end workflow, utilizes an improved statistical framework to identify transcriptomic binding sites of RNA-binding proteins more accurately, providing deeper insights into post-transcriptional gene regulation.