Article
Medicine, Research & Experimental
Rie Asada Kitamura, Kristina G. Maxwell, Wenjuan Ye, Kelly Kries, Cris M. Brown, Punn Augsornworawat, Yoel Hirsch, Martin M. Johansson, Tzvi Weiden, Joseph Ekstein, Joshua Cohen, Justin Klee, Kent Leslie, Anton Simeonov, Mark J. Henderson, Jeffrey R. Millman, Fumihiko Urano
Summary: Wolfram syndrome is a rare genetic disorder characterized by diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration, largely caused by mutations in the WFS1 gene. Recent studies have shown that Wolfram syndrome is a spectrum disorder and a genotype-phenotype correlation analysis is needed for diagnosis and treatment development. This study focused on a common WFS1 gene variant in the Ashkenazi Jewish population, which was associated with milder forms of Wolfram syndrome. By using induced pluripotent stem cells, the researchers found that a combination treatment of chemical chaperones could mitigate the detrimental effects caused by the variant and increase insulin secretion. Thus, this study provides a valuable platform for further genotype-phenotype analysis and therapeutic development for Wolfram syndrome.
Article
Biotechnology & Applied Microbiology
Jiseong Kim, Jin-Su Kim, Dohyun Kim, Alvin Bacero Bello, Byoung Ju Kim, Byung-Hyun Cha, Soo-Hong Lee
Summary: In this study, we successfully isolated mesenchymal stem cells (MSCs) from a condensed mass within teratomas generated from human induced pluripotent stem cells (iPSCs). Comprehensive assessments showed that iPSC-derived MSCs (iPSC-MSCs) exhibited characteristics and cell behaviors similar to conventional MSCs, including robust proliferative capabilities and the ability to differentiate into multiple lineages. Our findings suggest that teratomas are a promising source for isolating condensed MSCs, and iPSC-MSCs derived from teratomas have the potential for tissue regeneration.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Neurosciences
Kai Zhou, Jinming Han, Yafeng Wang, Yiran Xu, Yaodong Zhang, Changlian Zhu
Summary: Circulating monocytes can transform into bone marrow-derived macrophages (BMDMs) and play important roles in the central nervous system (CNS). Modulating BMDMs may be a way to treat neurological diseases, and BMDMs can serve as gene delivery vehicles after bone marrow transplantation. Understanding the roles of BMDMs in CNS diseases and their potential as gene delivery vehicles provides new opportunities for therapeutic interventions.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Neurosciences
Derek H. Oakley, Naomi Klickstein, Caitlin Commins, Mirra Chung, Simon Dujardin, Rachel E. Bennett, Bradley T. Hyman, Matthew P. Frosch
Summary: This study established an accelerated human neuronal model incorporating soluble tau species and tau aggregation, and showed that uptake of exogenous tau seeds increases the risk of neuronal death. Specific morphologic strains of Tau aggregation were identified to be associated with differing levels of neurotoxicity. Additionally, iPSC neurons expressing the PSEN1 L435F mutation exhibited accelerated Tau aggregation kinetics and a bias in tau strain propagation.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Peiying Deng, Liang Wang, Qiongqiong Zhang, Suhui Chen, Yamin Zhang, Hong Xu, Hui Chen, Yi Xu, Wei He, Jianmin Zhang, Hua Sun
Summary: This study investigated the effects and mechanisms of electroacupuncture (EA) combined with induced pluripotent stem cell-derived small extracellular vesicles (iPSC-EVs) on mice with ischemic stroke. The combination treatment improved neurological impairments, reduced infarct volume and neuronal apoptosis, and modulated immune responses. It also exerted neuroprotective effects by regulating the IL-33/ST2 axis and inhibiting microglia and astrocyte activation. These findings suggest that EA and iPSC-EVs have a synergistic neuroprotective effect and may be a promising therapy for ischemic stroke.
Article
Multidisciplinary Sciences
Christina Theodoris, Ping Zhou, Lei Liu, Yu Zhang, Tomohiro Nishino, Yu Huang, Aleksandra Kostina, Sanjeev S. Ranade, Casey A. Gifford, Vladimir Uspenskiy, Anna Malashicheva, Sheng Ding, Deepak Srivastava
Summary: By using a machine-learning approach, small molecules that can broadly correct dysregulated gene networks in a human heart disease model were identified, with the most efficacious candidate successfully preventing and treating AV disease in a mouse model.
Review
Neurosciences
Saumya Maheshwari, Gabriela Vilema-Enriquez, Richard Wade-Martins
Summary: Friedreich ataxia is a rare genetic disorder caused by a repeated expansion of GAA trinucleotide sequences. The use of induced pluripotent stem cells (iPSCs) has provided a valuable platform for studying the disease. iPSC-derived models enable the study of disease mechanisms and the testing of novel therapies for Friedreich ataxia.
TRANSLATIONAL NEURODEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Hae-Ri Lee, Soo Kim, Sungho Shin, Seon-Yeong Jeong, Dae-Won Lee, Sun-Ung Lim, Ji Yeon Kang, Mi-Young Son, Cheolju Lee, Kyung-Rok Yu, Myungshin Kim, Il-Hoan Oh
Summary: In this study, the transition from primary MSCs to iMSCs was characterized by increased proliferative activity and variations in differentiation potential. iMSCs exhibited unique gene and protein expression patterns, resembling pericyte-like cells, and showed enhanced self-renewal and immune suppression capabilities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Ali G. Turhan, Jinwook W. Hwang, Diana Chaker, Albert Tasteyre, Theodoros Latsis, Frank Griscelli, Christophe Desterke, Annelise Bennaceur-Griscelli
Summary: Advances in stem cell biology, particularly in the development of organoid technology, offer potential for cancer modeling, organ repair, and as experimental tools for studying infections like SARS-Cov-2. iPSC-derived organoids hold promise for the future of regenerative medicine and genomic editing.
FRONTIERS IN MEDICINE
(2021)
Article
Cell Biology
Domiziana Costamagna, Valerie Casters, Marc Beltra, Maurilio Sampaolesi, Anja Van Campenhout, Els Ortibus, Kaat Desloovere, Robin Duelen
Summary: This study generated in vitro human neuromuscular junctions (NMJs) using a microfluidic strategy from patient-specific induced pluripotent stem cell (hiPSC) lines to model disease-relevant neuropathologic processes in hereditary spastic paraplegia (HSP). The unique strength of this NMJ model is its ability to generate lower motor neurons (MNs) and myotubes from autologous hiPSC origin while maintaining the genetic background of HSP patient donors. The study found that HSP-derived lines exhibited axonal swellings, reduced levels of SPASTIN protein, and impaired NMJ profiles, offering unique tools to study the pathologic mechanisms of HSP.
Article
Medicine, General & Internal
Yaxun Sun, Jun Su, Xiaochen Wang, Jue Wang, Fengfeng Guo, Hangyuan Qiu, Hangping Fan, Dongsheng Cai, Hao Wang, Miao Lin, Wei Wang, Ye Feng, Guosheng Fu, Tingyu Gong, Ping Liang, Chenyang Jiang
Summary: This study investigated Brugada syndrome using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). By comparing the iPSC-CMs from patients with Brugada syndrome, asymptomatic mutation carriers, and healthy controls, it was found that patients exhibited more severe phenotypes while carriers had milder phenotypes. Genome editing effectively corrected the arrhythmic phenotype in patient iPSC-CMs.
Article
Cell & Tissue Engineering
Rebecca E. Schmitt, Douglas Y. Smith, Dong Seong Cho, Lindsey A. Kirkeby, Zachary T. Resch, Teerin Liewluck, Zhiyv Niu, Margherita Milone, Jason D. Doles
Summary: This study investigated the underlying mechanisms of GNE myopathy using a patient-derived induced pluripotent stem cell (iPSC) model. The findings revealed defects in myogenic progression and alterations in stress and autophagy signaling in GNE myopathy patient-derived iPSCs. Treatment with an autophagy activator improved myogenic differentiation in the patient-derived iPSCs.
NPJ REGENERATIVE MEDICINE
(2022)
Article
Cell & Tissue Engineering
Takahiro Kitagawa, Narihito Nagoshi, Yasuhiro Kamata, Momotaro Kawai, Kentaro Ago, Keita Kajikawa, Reo Shibata, Yuta Sato, Kent Imaizumi, Tomoko Shindo, Munehisa Shinozaki, Jun Kohyama, Shinsuke Shibata, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano
Summary: By inhibiting the neuronal activity of grafted cells, it was found that locomotor function in spinal cord injury mice significantly decreased. Trans-synaptic tracing revealed the integration of graft neurons into the host motor circuitry. These results indicate the importance of engrafting functionally competent neurons for the recovery from spinal cord injury.
Article
Chemistry, Medicinal
John R. Cashman, Daniel Ryan, Wesley L. McKeithan, Karl Okolotowicz, Jorge Gomez-Galeno, Mark Johnson, Kevin J. Sampson, Robert S. Kass, Arash Pezhouman, Hrayr S. Karagueuzian, Mark Mercola
Summary: Ventricular cardiac arrhythmia can occur in acquired or congenital heart disease. Long QT syndrome type-3 (LQT3) is a congenital form of VA caused by cardiac sodium channel SCN5A mutations. Mexiletine can inhibit I-NaL and shorten the QT interval, but can also prolong the cardiac action potential at therapeutic doses.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, General & Internal
Wenrui Ma, Jingjing Zhang, Shaowen Liu, Shiqiang Yan, Kehua Xu, Yu Shrike Zhang, Mieradilijiang Abudupataer, Yang Ming, Shichao Zhu, Bitao Xiang, Xiaonan Zhou, Shaman Luo, Hui Huang, Yuyi Tang, Shan Zhang, Zhuxin Xie, Nan Chen, Xiaoning Sun, Jun Li, Hao Lai, Chunsheng Wang, Kai Zhu, Weijia Zhang
Summary: This study developed a dynamic three-dimensional microphysiological model for studying thoracic aortic aneurysm (TAA) and drug discovery. The model successfully recapitulated the expressions of TAA-related genes and highlighted the disease characteristics of TAA. Drug testing demonstrated that metformin partially restored the function of TAA patients' cells. Mouse experiments and clinical investigations also supported the effectiveness of metformin in limiting aortic dilation.
Article
Biochemistry & Molecular Biology
Tomonori Tsuchida, Soichiro Murata, Koichiro Matsuki, Akihiro Mori, Megumi Matsuo, Satoshi Mikami, Satoshi Okamoto, Yasuharu Ueno, Tomomi Tadokoro, Yun-Wen Zheng, Hideki Taniguchi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell & Tissue Engineering
Jian-Yun Ge, Yun-Wen Zheng, Tomonori Tsuchida, Kinji Furuya, Hiroko Isoda, Hideki Taniguchi, Nobuhiro Ohkohchi, Tatsuya Oda
STEM CELL RESEARCH & THERAPY
(2020)
Article
Multidisciplinary Sciences
Yuanbin Song, Liang Shan, Rana Gbyli, Wei Liu, Till Strowig, Amisha Patel, Xiaoying Fu, Xiaman Wang, Mina L. Xu, Yimeng Gao, Ashley Qin, Emanuela M. Bruscia, Toma Tebaldi, Giulia Biancon, Padmavathi Mamillapalli, David Urbonas, Elizabeth Eynon, David G. Gonzalez, Jie Chen, Diane S. Krause, Jonathan Alderman, Stephanie Halene, Richard A. Flavell
Summary: This immunodeficient murine model with combined human liver and cytokine humanization enhances human erythropoiesis and RBC survival in circulation. It can be used to study diseases affecting RBCs and replicate acute sickle cell disease pathology.
Review
Cell & Tissue Engineering
Meng-Xue Xu, Li-Ping Liu, Yu-Mei Li, Yun-Wen Zheng
Summary: Platelet transfusion is a standard clinical treatment to prevent bleeding, but the shortage of supply and challenges such as short shelf life and allogeneic immunity call for the development of alternative sources. Human pluripotent stem cells offer a potential unlimited source for regenerative medicine and research models for disease pathogenesis. Research efforts are focused on generating functional induced platelets from hPSCs and evaluating their production efficiency and safety concerns.
STEM CELLS INTERNATIONAL
(2021)
Article
Medicine, Research & Experimental
Kinji Furuya, Yun-Wen Zheng, Jian-Yun Ge, Ludi Zhang, Tomoaki Furuta, Chen Liang, Haruna Abe, Hiroya Yagi, Hiromi Hamada, Hiroko Isoda, Lijian Hui, Nobuhiro Ohkohchi, Tatsuya Oda
Summary: The human-to-rat hematopoietic stem cell transplantation model demonstrated the importance of controlling macrophages to prolong the survival of human cells in rats. This model could be valuable for future xenotransplantation research and clinical studies.
XENOTRANSPLANTATION
(2021)
Article
Chemistry, Multidisciplinary
Ludi Zhang, Jian-Yun Ge, Yun-Wen Zheng, Zhen Sun, Chenhua Wang, Zhaoliang Peng, Baihua Wu, Mei Fang, Kinji Furuya, Xiaolong Ma, Yanjiao Shao, Nobuhiro Ohkohchi, Tatsuya Oda, Jianglin Fan, Guoyu Pan, Dali Li, Lijian Hui
Summary: Liver-humanized rats were generated using CRISPR/Cas9 technology, with an optimized liver injury preconditioning protocol leading to increased human hepatocyte repopulation in the rat livers. This model is preferred for pharmacological studies and human hepatocyte production, showcasing potential for pharmacokinetic profiling of human-specific metabolites and informative implications for hepatocyte transplantation in other large-sized species.
Article
Gastroenterology & Hepatology
Hui Xu, Yu-Mei Li, Yongxiang Yi, Yun-Wen Zheng, Nobuhiro Ohkohchi
Summary: The study found that platelet transfusion for cirrhotic patients after liver resection is safe, but no significant improvement in liver function was observed.
CASE REPORTS IN GASTROINTESTINAL MEDICINE
(2021)
Review
Cell & Tissue Engineering
Hang Zhou, Yun Wang, Li-Ping Liu, Yu-Mei Li, Yun-Wen Zheng
Summary: The rapid development of gene-editing technology has broadened the applications of pluripotent stem cells (PSCs) and their derived organoids in regenerative medicine. Despite ethical concerns and safety risks, PSC gene editing continues to benefit mankind at an unprecedented rate.
STEM CELLS INTERNATIONAL
(2021)
Article
Cell Biology
Li-Ping Liu, Dong-Xu Zheng, Zheng-Fang Xu, Hu-Cheng Zhou, Yun-Cong Wang, Hang Zhou, Jian-Yun Ge, Daisuke Sako, Mi Li, Kazunori Akimoto, Yu-Mei Li, Yun-Wen Zheng
Summary: This study reveals the commonalities and differences between amniotic epithelial stem cells (AESCs) and keratinocytes (KCs) through transcriptomics analysis and functional evaluation. The analysis shows that AESCs are involved in epidermis-associated biological processes shared with KCs, but they also exhibit distinct features. The overexpression of TP63 and activation of NOTCH signaling can enhance AESC stemness and improve their differentiation features.
Article
Oncology
Rana Gbyli, Yuanbin Song, Wei Liu, Yimeng Gao, Giulia Biancon, Namrata S. Chandhok, Xiaman Wang, Xiaoying Fu, Amisha Patel, Ranjini Sundaram, Toma Tebaldi, Padmavathi Mamillapalli, Amer M. Zeidan, Richard A. Flavell, Thomas Prebet, Ranjit S. Bindra, Stephanie Halene
Summary: Treatment options for relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients are limited. Our study demonstrates the effectiveness of the PARP inhibitor olaparib in IDH1/2-mutant AML/MDS patients, particularly those who are resistant to IDH(m)i treatment or have relapsed.
Article
Biochemistry & Molecular Biology
Giulia Biancon, Poorval Joshi, Joshua T. Zimmer, Torben Hunck, Yimeng Gao, Mark D. Lessard, Edward Courchaine, Andrew E. S. Barentine, Martin Machyna, Valentina Botti, Ashley Qin, Rana Gbyli, Amisha Patel, Yuanbin Song, Lea Kiefer, Gabriella Viero, Nils Neuenkirchen, Haifan Lin, Joerg Bewersdorf, Matthew D. Simon, Karla M. Neugebauer, Toma Tebaldi, Stephanie Halene
Summary: Splicing factor mutations, especially in U2AF1, are common drivers of myeloid malignancies, affecting the splicing process and leading to intron retention and exon exclusion. In addition, U2AF1 mutations directly influence the components of stress granules, which are involved in adaptive oncogenic strategies in cancer cells.
Article
Multidisciplinary Sciences
Chenbo Ding, Hao Xu, Zhibin Yu, Manolis Roulis, Rihao Qu, Jing Zhou, Joonseok Oh, Jason Crawford, Yimeng Gao, Ruaidhri Jackson, Esen Sefik, Simiao Li, Zheng Wei, Mathias Skadow, Zhinan Yin, Xinshou Ouyang, Lei Wang, Qiang Zou, Bing Su, Weiguo Hu, Richard A. Flavell, Hua-Bing Li
Summary: This study found that ALKBH5 and m(6)A modification are involved in the development of γδT cells. Depletion of ALKBH5 leads to an expansion of γδT cells, resulting in enhanced protection against Salmonella typhimurium infection in the gastrointestinal tract. This is attributed to the increased development of γδT cell precursors and the reduced expression of target genes in the Notch signaling pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Dongxu Zheng, Annelot Wondergem, Susan Kloet, Iris Willemsen, Judit Balog, Stephen J. Tapscott, Ahmed Mahfouz, Anita van den Heuvel, Silvere M. van der Maarel
Summary: In this study, single-nucleus RNA-sequencing was used to investigate the cellular heterogeneity in FSHD. Two distinct populations of DUX4-affected nuclei were identified, and the study revealed transcriptomic differences and shared features with early embryonic cells.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemical Research Methods
Yimeng Gao, Shirui Chen, Stephanie Halene, Toma Tebaldi
Summary: The presence of dsRNAs in cells plays multiple regulatory functions, with viral dsRNAs activating innate immune responses. Alterations in RNA editing and modifications can lead to accumulation of abnormal endogenous dsRNAs and trigger harmful innate immune responses. This study provides a complete protocol for measuring dsRNAs in live mouse tissue using dsRNA immunoprecipitation and sequencing, focusing on tissue isolation, immunoprecipitation, and computational analysis.
