Article
Veterinary Sciences
Abinaya Chandrasekaran, Barbara Blicher Thomsen, Jorgen Steen Agerholm, Lais Vicari de Figueiredo Pessoa, Naira Caroline Godoy Pieri, Vahideh Sabaghidarmiyan, Katarina Langley, Miriam Kolko, Andre Furugen Cesar de Andrade, Fabiana Fernandes Bressan, Poul Hyttel, Mette Berendt, Kristine Freude
Summary: Domestic dogs are considered superior models for translational medicine, particularly in the field of neurodegenerative medicine. The generation of canine induced pluripotent stem cells provides a potential method for developing in vitro models for neurodegenerative diseases. However, challenges and new perspectives must be considered before utilizing the canine model in translational neurological studies, as shown by the differences encountered in neural differentiation potential during this study.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Emma Veronica Carsana, Matteo Audano, Silvia Breviario, Silvia Pedretti, Massimo Aureli, Giulia Lunghi, Nico Mitro
Summary: In recent years, induced pluripotent stem cell-based neuronal models have provided new insights into the study and treatment of neurological diseases. This study demonstrates the metabolic rewiring that occurs during the differentiation stages of dopaminergic neurons, highlighting the reliance of induced pluripotent stem cells on fatty acid beta-oxidation as a fuel source and the preferential catabolism of glucose in mature neurons.
Article
Cell Biology
Ram Sagar, Ioannis Azoidis, Cristina Zivko, Ariadni Xydia, Esther S. Oh, Paul B. Rosenberg, Constantine G. Lyketsos, Vasiliki Mahairaki, Dimitrios Avramopoulos
Summary: Recent advances in generating pluripotent stem cells from somatic cells and differentiating them into various cell types have allowed us to study these cells without the limitations of disease-related changes. By creating induced pluripotent stem cells (iPSCs) from Alzheimer's disease (AD) patients and controls, and differentiating them into glutamatergic neurons, our RNA sequencing analysis identified 621 differentially expressed genes between AD and control neurons. These genes have significant overlap with those reported in a single-cell transcriptome study of AD patients, including five genes associated with AD from genome-wide association studies, suggesting their involvement in a larger functional network.
Article
Biotechnology & Applied Microbiology
Zongyou Guo, Chi-Kun Tong, Joanna Jackow, Yanne S. Doucet, Hasan E. Abaci, Wangyong Zeng, Corey Hansen, Ryota Hayashi, Dominick DeLorenzo, Avina Rami, Alberto Pappalardo, Ellen A. Lumpkin, Angela M. Christiano
Summary: Researchers have successfully differentiated itch sensory neuron-like cells from iPSC lines and innervated them into full thickness human skin constructs, providing new possibilities for the treatment and drug development of skin diseases such as atopic dermatitis.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Giulia Paolini Sguazzi, Valentina Muto, Marco Tartaglia, Enrico Bertini, Claudia Compagnucci
Summary: Gene therapy traditionally used viral vectors for gene delivery, but recent advances in stem cell and gene therapy fields have revolutionized this approach, particularly with the combination of stem cell replacement therapy and gene editing technology, leading to a new era in gene therapy for neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yue Su, Ling Wang, Zhiqiang Fan, Ying Liu, Jiaqi Zhu, Deborah Kaback, Julia Oudiz, Tayler Patrick, Siu Pok Yee, Xiuchun (Cindy) Tian, Irina Polejaeva, Young Tang
Summary: This study successfully generated biPSCs with long-term self-renewal capacity and pluripotent characteristics from bovine mesenchymal stem cells. The cells exhibited morphological changes under different culture conditions, and transcriptome analysis showed high similarity to bovine ESCs and embryos. The naive-like biPSCs also demonstrated the ability to integrate into extra-embryonic tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Arvind Kumar Shukla, Ge Gao, Byoung Soo Kim
Summary: Induced pluripotent stem cells (iPSCs) are generated by genetic reprogramming of adult cells and have high safety. They have significant potential in tissue engineering and 3D bioprinting technology plays a vital role in this field by applying undifferentiated and differentiated iPSCs.
Article
Cell & Tissue Engineering
Chuti Laowtammathron, Chanchao Lorthongpanich, Nittaya Jiamvoraphong, Pimonwan Srisook, Phatchanat Klaihmon, Pakpoom Kheolamai, Sudjit Luanpitpong, Surapol Issaragrisil
Summary: The study explores the role of YAP in hematopoietic differentiation of hiPSCs. It is found that suppressing YAP activity enhances the efficiency of hematopoietic differentiation and increases the yield of HSPCs.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Cell Biology
Shuai Yu, Rui Zhang, Qiaoyan Shen, Zhenshuo Zhu, Juqing Zhang, Xiaolong Wu, Wenxu Zhao, Na Li, Fan Yang, Hongjiang Wei, Jinlian Hua
Summary: By overexpressing the transcription factor ESRRB, flat, monolayered piPSCs were created with enhanced chimeric capacity into the trophectoderm. ESRRB directly regulates the expressions of trophoblast stem cell markers, and its cooperation with OCT4 facilitates the transition from pluripotent state to trophoblast-like state.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell & Tissue Engineering
Azam Shamsian, Roxana Sahebnasagh, Amir Norouzy, Safin Hassan Hussein, Mohammad Hossein Ghahremani, Zahra Azizi
Summary: Induced pluripotent stem cells (iPSCs) have wide-ranging potential applications in medical research, and cancer cells may serve as a new source for generating iPSCs. Although cancer cells share similarities with iPSCs, they carry genetic abnormalities and pose a risk of tumor formation. This review discusses the feasibility of using cancer cells as a preferred source for iPSC generation.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Cell Biology
Na Yu, Jin Qiu, Kaijing Li, Qian Luo, Xuan Liu, Ying Yang, Zihua Jiang, Shengyu He, Anqi He, Shuilian Chen, Xi Chen, Yan Li, Jian Ge, Jing Zhuang, Keming Yu
Summary: This study compares the DNA stability between primary neurons and differentiated neurons. The researchers found that iPSCs-derived neurons have a higher basal level of gamma-H2AX phosphorylation compared to primary retinal neurons. However, iPSCs-derived neurons are more sensitive to UV treatment. The expression of Ku80 and Ku70 in stem cell-derived neurons promotes DNA stability and cell viability.
CELL BIOLOGY INTERNATIONAL
(2022)
Review
Biochemistry & Molecular Biology
Agnieszka Fus-Kujawa, Barbara Mendrek, Anna Trybus, Karolina Bajdak-Rusinek, Karolina L. Stepien, Aleksander L. Sieron
Summary: Induced pluripotent stem cells (iPSCs) show potential in gene therapy and disease modeling. To safely apply this technology in clinical settings, optimal reprogramming factors and vectors must be considered to reduce the risk of insertional tumorigenesis.
Review
Neurosciences
Anindita Bose, Gregory A. Petsko, Lorenz Studer
Summary: Parkinson's disease is the second most prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. Recent advances in stem cell technology have contributed to understanding the disease mechanisms and identifying new therapeutic targets, but more research is needed to model the age-related aspects of the disease and understand the interactions among disease-modifying genes and between genetic and environmental contributions.
TRENDS IN NEUROSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
S. Bindhya, C. Sidhanth, S. Krishnapriya, Manoj Garg, T. S. Ganesan
Summary: The study demonstrates that ovarian cancer cell line PEO4 can be reprogrammed into iPSCs using GLIS1 as a transcription factor instead of MYC, expressing CSCs markers and showing increased drug resistance. Additionally, normal fallopian tube epithelial cells can also be transformed into iPSCs using the same method in vitro.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Cell Biology
Yeonmi Lee, Minchul Kim, Miju Lee, Seongjun So, Soon-Suk Kang, Jiwan Choi, Deokhoon Kim, Hyohoon Heo, Sung Soo Lee, Hee Ra Park, Jung Jae Ko, Jihwan Song, Eunju Kang
Summary: This study demonstrates that mtDNA mutations in patients with AD could lead to mitochondrial dysfunction and accelerated A beta deposition. Early screening for mtDNA mutations in iPSC lines would be essential for developing autologous cell therapy or drug screening for patients with AD.
CELL PROLIFERATION
(2022)
Article
Neurosciences
Simon T. Schafer, Apua C. M. Paquola, Shani Stern, David Gosselin, Manching Ku, Monique Pena, Thomas J. M. Kuret, Marvin Liyanage, Abed AlFatah Mansour, Baptiste N. Jaeger, Maria C. Marchetto, Christopher K. Glass, Jerome Mertens, Fred H. Gage
NATURE NEUROSCIENCE
(2019)
Review
Biochemistry & Molecular Biology
Larissa Traxler, Frank Edenhofer, Jerome Mertens
Review
Biochemistry & Molecular Biology
Anita Erharter, Sandra Rizzi, Jerome Mertens, Frank Edenhofer
Review
Geriatrics & Gerontology
Johannes C. M. Schlachetzki, Tomohisa Toda, Jerome Mertens
EXPERIMENTAL GERONTOLOGY
(2020)
Editorial Material
Cell & Tissue Engineering
Joseph R. Herdy, Lukas Karbacher, Jerome Mertens
Summary: Researchers dissect the process of converting human somatic cells into iNs into two largely independent steps and identify key players in each stage.
Article
Cell & Tissue Engineering
Jerome Mertens, Joseph R. Herdy, Larissa Traxler, Simon T. Schafer, Johannes C. M. Schlachetzki, Lena Bohnke, Dylan A. Reid, Hyungjun Lee, Dina Zangwill, Diana P. Fernandes, Ravi K. Agarwal, Raffaella Lucciola, Lucia Zhou-Yang, Lukas Karbacher, Frank Edenhofer, Shani Stern, Steve Horvath, Apua C. M. Paquola, Christopher K. Glass, Shauna H. Yuan, Manching Ku, Attila Szucs, Lawrence S. B. Goldstein, Douglas Galasko, Fred H. Gage
Summary: Our study identifies AD-related neuronal changes as age-dependent cellular programs that impair neuronal identity.
Review
Cell Biology
Larissa Traxler, Jessica Lagerwall, Sophie Eichhorner, Davide Stefanoni, Angelo D'Alessandro, Jerome Mertens
Summary: An uninterrupted energy supply is crucial for the optimal functioning of all organs, particularly the human brain which is highly energy dependent. Research in neuroscience focuses on energy metabolic pathways, as genetic defects in oxidative phosphorylation mechanism contribute towards neurodevelopmental disorders and changes in glucose metabolism are observed in neurodegenerative disorders. Recent studies have shown that metabolism plays a vital role in cell fate and function, impacting diseases of the brain.
DISEASE MODELS & MECHANISMS
(2021)
Article
Cell Biology
Abhinav Soni, Diana Kluetsch, Xin Hu, Judith Houtman, Nicole Rund, Asako McCloskey, Jerome Mertens, Simon T. Schafer, Hayder Amin, Tomohisa Toda
Summary: The study employed a method combining neural stem cell culture and direct cell type conversion to efficiently generate functional neurons, offering opportunities for investigating plasticity mechanisms, drug screening assays, and probing the molecular and biophysical basis of neurodevelopmental and neurodegenerative diseases.
Article
Cell & Tissue Engineering
Lena Boehnke, Lucia Zhou-Yang, Silvia Pelucchi, Flora Kogler, Daniela Frantal, Florian Schoen, Stina Lagerstroem, Oliver Borgogno, Jennifer Baltazar, Joseph R. Herdy, Sarah Kittel-Schneider, Michaela Defrancesco, Jerome Mertens
Summary: Direct conversion of human skin fibroblasts into induced neurons is a useful technology for generating donor-specific human neurons. Researchers have identified ALK2 as a potential replacement for recombinant Noggin, which is commonly used in the conversion protocol. The ALK2 inhibitor DMH1 enhances conversion efficiency and yields high-purity neuronal cultures at a lower cost compared to traditional methods.
CELLULAR REPROGRAMMING
(2022)
Article
Cell Biology
Larissa Traxler, Joseph R. Herdy, Davide Stefanoni, Sophie Eichhorner, Silvia Pelucchi, Attila Szucs, Alice Santagostino, Yongsung Kim, Ravi K. Agarwal, Johannes C. M. Schlachetzki, Christopher K. Glass, Jessica Lagerwall, Douglas Galasko, Fred H. Gage, Angelo D'Alessandro, Jerome Mertens
Summary: This study investigated the metabolic changes and transcriptional alterations in sporadic Alzheimer's disease (AD) utilizing induced neurons (iNs) from AD patients. The pathological isoform switching of PKM2 was found to contribute to neuronal vulnerability and loss in AD. Chemical modulation of PKM2 could reverse these changes and enhance neuronal resilience against cell death.
Article
Neurosciences
Mark van den Hurk, Shong Lau, Maria C. Marchetto, Jerome Mertens, Shani Stern, Olga Corti, Alexis Brice, Beate Winner, Juergen Winkler, Fred H. Gage, Cedric Bardy
Summary: This study investigated the gene dysregulation in live midbrain neurons reprogrammed from the skin cells of Parkinson's disease (PD) patients. The results showed dysregulation of genes involved in synaptic transmission, metabolism, and cellular stress/immune responses in PD. The study also identified pesticides and endoplasmic reticulum stressors as significant gene-chemical interactions in PD. Additionally, the researchers associated the PD transcriptomic profile with candidate pharmaceuticals in a large database and clinical trials registry.
NPJ PARKINSONS DISEASE
(2022)
Article
Cell & Tissue Engineering
Joseph R. Herdy, Larissa Traxler, Ravi K. Agarwal, Lukas Karbacher, Johannes C. M. Schlachetzki, Lena Boehnke, Dina Zangwill, Doug Galasko, Christopher K. Glass, Jerome Mertens, Fred H. Gage
Summary: The concept of senescence extends beyond proliferating cells, as senescence-like features have been observed in neurons, including those affected by Alzheimer's disease. Targeting senescent neurons could be a strategy for preventing or treating AD.
Review
Pharmacology & Pharmacy
Alerie G. de la Fuente, Silvia Pelucchi, Jerome Mertens, Monica Di Luca, Daniela Mauceri, Elena Marcello
Summary: Ageing is the main risk factor for most primary neurodegenerative disorders, and protein misfolding and toxic protein accumulation are considered causative events. However, other biological pathways affected by brain ageing also contribute to pathogenesis. This article discusses the involvement of mechanisms controlling neuronal structure, gene expression, autophagy, cell metabolism, and neuroinflammation in the onset and progression of neurodegenerative disorders, and reviews therapeutic strategies aiming to normalize these pathways for increased brain resilience.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Clinical Neurology
Larissa Traxler, Raffaella Lucciola, Joseph R. R. Herdy, Jeffrey R. R. Jones, Jerome Mertens, Fred H. H. Gage
Summary: Most age-related neurodegenerative diseases remain incurable due to an incomplete understanding of the disease mechanisms. Cellular state shifts play an important role in sustaining the function and resilience of the young brain, but excessive state shifts in the aged brain might lead to pathological fate loss and neurodegeneration.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Cell Biology
Cristina Marisol Castillo Bautista, Kristin Eismann, Marc Gentzel, Silvia Pelucchi, Jerome Mertens, Hannah E. Walters, Maximina H. Yun, Jared Sterneckert
Summary: Aging disrupts protein homeostasis and contributes to various diseases, including ALS. Repressing autophagy is a strategy to restore protein homeostasis and protect neurons. A study found that obatoclax, a small molecule BH3 mimetic, can disrupt the interaction between BECN1 and BCL2, reducing FUS levels and improving protein homeostasis to rescue neurons. Obatoclax has potential as a therapeutic for ALS and other age-related disorders linked to protein homeostasis defects.
