Article
Cell Biology
Baofeng Feng, Asiamah Ernest Amponsah, Ruiyun Guo, Xin Liu, Jinyu Zhang, Xiaofeng Du, Zijing Zhou, Jingjing He, Jun Ma, Huixian Cui
Summary: The study suggests that aberrant cytokine secretion by astrocytes derived from induced pluripotent stem cells (iPSCs) of amyotrophic lateral sclerosis (ALS) patients is regulated by the mTOR-autophagy pathway. Activating autophagy could reduce cytokine secretion by ALS astrocytes, potentially mitigating their toxic effects on motor neurons.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Neurosciences
Nina M. Drager, Sydney M. Sattler, Cindy Tzu-Ling Huang, Olivia M. Teter, Kun Leng, Sayed Hadi Hashemi, Jason Hong, Giovanni Aviles, Claire D. Clelland, Lihong Zhan, Joe C. Udeochu, Lay Kodama, Andrew B. Singleton, Mike A. Nalls, Justin Ichida, Michael E. Ward, Faraz Faghri, Li Gan, Martin Kampmann
Summary: This study presents a screening platform to systematically elucidate the functional consequences of genetic perturbations in human induced pluripotent stem cell-derived microglia. The researchers identified genes controlling microglia survival, activation, and phagocytosis, as well as disease-associated genes. They also determined regulators of disease-relevant microglial states using single-cell RNA sequencing. The platform has the potential for therapeutic targeting and functional characterization of microglia.
NATURE NEUROSCIENCE
(2022)
Article
Cell Biology
Maria Jose Castellanos-Montiel, Mathilde Chaineau, Anna Kristyna Franco-Flores, Ghazal Haghi, Dulce Carrillo-Valenzuela, Wolfgang E. E. Reintsch, Carol X. -Q. Chen, Thomas M. M. Durcan
Summary: Researchers have developed a three-dimensional model and optimized a workflow for its morphological, gene expression, protein, and functional profiling.
Article
Cell & Tissue Engineering
Yuta Tsujisaka, Takeshi Hatani, Chikako Okubo, Ryo Ito, Azuma Kimura, Megumi Narita, Kazuhisa Chonabayashi, Shunsuke Funakoshi, Antonio Lucena-Cacace, Taro Toyoda, Kenji Osafune, Takeshi Kimura, Hirohide Saito, Yoshinori Yoshida
Summary: By combining miR-switch with MACS technology, we have developed a rapid and efficient method for purifying large amounts of PSC-derived cells. This method can detect specific miRNAs in target cells and use CD4 transgene as a selection marker for MACS, achieving cell purification.
Article
Biochemistry & Molecular Biology
Hadas Ben-Zvi, Tatiana Rabinski, Rivka Ofir, Smadar Cohen, Gad D. Vatine
Summary: The mutation of PLEKHM2[delAG] causes dilated cardiomyopathy with left ventricular non-compaction and is involved in the functional development of neurons through the regulation of autophagic flux.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mafalda Rizzuti, Valentina Melzi, Delia Gagliardi, Davide Resnati, Megi Meneri, Laura Dioni, Pegah Masrori, Nicole Hersmus, Koen Poesen, Martina Locatelli, Fabio Biella, Rosamaria Silipigni, Valentina Bollati, Nereo Bresolin, Giacomo Pietro Comi, Philip Van Damme, Monica Nizzardo, Stefania Corti
Summary: This study revealed the dysregulation of microRNA (miRNA) in amyotrophic lateral sclerosis (ALS), suggesting that miRNA analysis could be a promising tool for understanding the molecular mechanisms underlying this disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Medicinal
Saima Jalil Imran, Barbora Vagaska, Jan Kriska, Miroslava Anderova, Mario Bortolozzi, Gino Gerosa, Patrizia Ferretti, Radim Vrzal
Summary: Exposure to environmental pollutants and endogenous metabolites may affect cognitive development and motor function. In this study, human motor neurons generated from hiPSCs were used as an in vitro model to investigate the effects of AhR ligands on the expression of AhR pathway components. The results suggest that the expression of AhR signaling components is regulated with neuronal differentiation and is differently affected by TCDD and other AhR ligands in human motor neurons.
Article
Food Science & Technology
Maren Schenke, Helene-Christine Prause, Wiebke Bergforth, Adina Przykopanski, Andreas Rummel, Frank Klawonn, Bettina Seeger
Summary: The research explores the use of human motor neurons generated from induced pluripotent stem cells for BoNT potency testing. Compared to the use of neuroblastoma cells, human neurons demonstrate higher sensitivity to BoNT serotypes A1 and B1, showing responses reflective of human sensitivity.
Article
Biochemistry & Molecular Biology
Jessie W. Brunner, Hanna C. A. Lammertse, Annemiek A. van Berkel, Frank Koopmans, Ka Wan Li, August B. Smit, Ruud F. Toonen, Matthijs Verhage, Sophie van der Sluis
Summary: This study compares different designs and statistical analysis methods used in iPSC research, and finds that commonly used case-control designs are generally underpowered. The study suggests that multiple isogenic pair designs can increase power and require fewer lines. A free web tool is provided for exploring the power of different study designs using any (pilot) data.
MOLECULAR PSYCHIATRY
(2023)
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
Cell & Tissue Engineering
Satoru Morimoto, Shinichi Takahashi, Daisuke Ito, Yugaku Date, Kensuke Okada, Chris Kato, Shiho Nakamura, Fumiko Ozawa, Chai Muh Chyi, Ayumi Nishiyama, Naoki Suzuki, Koki Fujimori, Tosho Kondo, Masaki Takao, Miwa Hirai, Yasuaki Kabe, Makoto Suematsu, Masahiro Jinzaki, Masashi Aoki, Yuto Fujiki, Yasunori Sato, Norihiro Suzuki, Jin Nakahara, Hideyuki Okano
Summary: A phase 1/2a trial of ropinirole in ALS, based on iPSC-based drug discovery, showed that ropinirole could slow down disease progression and prolong disease-progression-free survival in ALS patients. The study also revealed the potential involvement of dopamine D2 receptor and SREBP2-cholesterol pathway in the therapeutic effects of ropinirole.
Article
Biology
Federica Cordella, Laura Ferrucci, Chiara D'Antoni, Silvia Ghirga, Carlo Brighi, Alessandro Soloperto, Ylenia Gigante, Davide Ragozzino, Paola Bezzi, Silvia Di Angelantonio
Summary: Homeostatic plasticity is a form of synaptic plasticity where neurons respond to chronically altered network activity to maintain healthy brain function. In this study, an in vitro human cortical model system was developed using induced pluripotent stem cells, revealing the presence of homeostatic plasticity in human neuronal networks for the first time. This platform provides a versatile model for assessing human neural plasticity under physiological and pathological conditions, particularly in patients with neurodevelopmental and neurodegenerative diseases.
Article
Biology
Martin L. Tomov, Alison O'Neil, Hamdah S. Abbasi, Beth A. Cimini, Anne E. Carpenter, Lee L. Rubin, Mark Bathe
Summary: The study utilizes PRISM technology for multiplexed imaging analysis of iPSC-derived neural cultures to understand neural cell differentiation and disease models. The method is amenable to automation and scalability to multiple protein targets and samples.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biology
Catarina Catela, Yihan Chen, Yifei Weng, Kailong Wen, Paschalis Kratsios
Summary: This study identified the transcriptome of spinal motor neurons (MNs) in mice during embryonic and postnatal stages and discovered novel genes and transcription factors related to terminal differentiation. It was found that homeodomain transcription factors, including Hoxc8, played a crucial role in maintaining the expression of terminal differentiation markers in MNs. These findings provide insights into the evolutionary role of Hox in neuronal terminal differentiation.
Article
Multidisciplinary Sciences
Aaron M. Earley, Lena F. Burbulla, Dimitri Krainc, Rajeshwar Awatramani
Summary: Using single cell RNA sequencing, the study unraveled graded molecular identities during human neurogenesis from pluripotent stem cells. Differentiation platforms were established to model neural induction from stem cells, and the differentiated cell types were characterized by 10x single cell RNA sequencing.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Emily G. Baxi, Terri Thompson, Jonathan Li, Julia A. Kaye, Ryan G. Lim, Jie Wu, Divya Ramamoorthy, Leandro Lima, Vineet Vaibhav, Andrea Matlock, Aaron Frank, Alyssa N. Coyne, Barry Landin, Loren Ornelas, Elizabeth Mosmiller, Sara Thrower, S. Michelle Farr, Lindsey Panther, Emilda Gomez, Erick Galvez, Daniel Perez, Imara Meepe, Susan Lei, Berhan Mandefro, Hannah Trost, Louis Pinedo, Maria G. Banuelos, Chunyan Liu, Ruby Moran, Veronica Garcia, Michael Workman, Richie Ho, Stacia Wyman, Jennifer Roggenbuck, Matthew B. Harms, Jennifer Stocksdale, Ricardo Miramontes, Keona Wang, Vidya Venkatraman, Ronald Holewenski, Niveda Sundararaman, Rakhi Pandey, Danica-Mae Manalo, Aneesh Donde, Nhan Huynh, Miriam Adam, Brook T. Wassie, Edward Vertudes, Naufa Amirani, Krishna Raja, Reuben Thomas, Lindsey Hayes, Alex Lenail, Aianna Cerezo, Sarah Luppino, Alanna Farrar, Lindsay Pothier, Carolyn Prina, Todd Morgan, Arish Jamil, Sarah Heintzman, Jennifer Jockel-Balsarotti, Elizabeth Karanja, Jesse Markway, Molly McCallum, Ben Joslin, Deniz Alibazoglu, Stephen Kolb, Senda Ajroud-Driss, Robert Baloh, Daragh Heitzman, Tim Miller, Jonathan D. Glass, Natasha Leanna Patel-Murray, Hong Yu, Ervin Sinani, Prasha Vigneswaran, Alexander V. Sherman, Omar Ahmad, Promit Roy, Jay C. Beavers, Steven Zeiler, John W. Krakauer, Carla Agurto, Guillermo Cecchi, Mary Bellard, Yogindra Raghav, Karen Sachs, Tobias Ehrenberger, Elizabeth Bruce, Merit E. Cudkowicz, Nicholas Maragakis, Raquel Norel, Jennifer E. Van Eyk, Steven Finkbeiner, James Berry, Dhruv Sareen, Leslie M. Thompson, Ernest Fraenkel, Clive N. Svendsen, Jeffrey D. Rothstein
Summary: Answer ALS is a resource that includes patient-derived iPS cell lines, multi-omic data from iPS neurons, and clinical and smartphone data from over 1,000 ALS patients. This data can be used to identify distinct disease subgroups in ALS.
NATURE NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Wensen Jiang, Juliane D. Glaeser, Khosrowdad Salehi, Giselle Kaneda, Pranav Mathkar, Anton Wagner, Ritchie Ho, Dmitriy Sheyn
Summary: The study generated cell atlases of human intervertebral discs (IVDs) in both neonatal and adult stages and analyzed their composition, distribution, and function. Comparison of the cell atlases revealed the existence of different cell populations and their developmental trajectories. The findings provide insights into the cellular biology of IVDs and may have implications for the development of novel therapeutic targets for IVD degeneration.
Article
Clinical Neurology
Elke Braems, Valerie Bercier, Evelien Van Schoor, Kara Heeren, Jimmy Beckers, Laura Fumagalli, Lieselot Dedeene, Matthieu Moisse, Ilse Geudens, Nicole Hersmus, Arpan R. Mehta, Bhuvaneish T. Selvaraj, Siddharthan Chandran, Ritchie Ho, Dietmar R. Thal, Philip Van Damme, Bart Swinnen, Ludo Van Den Bosch
Summary: This study demonstrates the important roles of HNRNPK and RRM2 in C9orf72 ALS, revealing the link between RNA toxicity mechanism and aberrant DNA damage response. It provides new avenues for the treatment of C9orf72 ALS/FTD.
ACTA NEUROPATHOLOGICA
(2022)
Article
Neurosciences
Daniel Sommer, Sandeep Rajkumar, Mira Seidel, Amr Aly, Albert Ludolph, Ritchie Ho, Tobias M. Boeckers, Alberto Catanese
Summary: This study combines high definition multielectrode array techniques and transcriptomic analysis to investigate how impaired synaptic activity contributes to motor neuron degeneration in amyotrophic lateral sclerosis (ALS), providing insights into the pathogenesis of this neurodegenerative disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Wenting Guo, Haibo Wang, Arun Kumar Tharkeshwar, Julien Couthouis, Elke Braems, Pegah Masrori, Evelien Van Schoor, Yannan Fan, Karan Ahuja, Matthieu Moisse, Maarten Jacquemyn, Rodrigo Furtado Madeiro da Costa, Madhavsai Gajjar, Sriram Balusu, Tine Tricot, Laura Fumagalli, Nicole Hersmus, Rekin's Janky, Francis Impens, Pieter Vanden Berghe, Ritchie Ho, Dietmar Rudolf Thal, Rik Vandenberghe, Muralidhar L. Hegde, Siddharthan Chandran, Bart De Strooper, Dirk Daelemans, Philip Van Damme, Ludo Van den Bosch, Catherine Verfaillie
Summary: In this study, we identified NEK6 as a novel therapeutic target for C9orf72 FTD/ALS by performing a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell-derived cortical neurons. NEK6 was found to regulate poly(PR)-mediated p53-related DNA damage.
ALZHEIMERS & DEMENTIA
(2023)
Meeting Abstract
Hematology
Joshua P. Sasine, Jennifer Dukov, Dana Tran, Heather A. Himburg, Natalia Kozlova, Michelle Li, Jenny Kan, Mary Sehl, Gary J. Schiller, Ritchie Ho, Brijesh Singh, Bryanna Reinhardt, Peibin Yue, Christina Termini, Elena Pasquale, John P. Chute
Article
Multidisciplinary Sciences
Andrea Matlock, Vineet Vaibhav, Ronald Holewinski, Vidya Venkatraman, Victoria Dardov, Danica-Mae Manalo, Brandon Shelley, Loren Ornelas, Maria Banuelos, Berhan Mandefro, Renan Escalante-Chong, Jonathan Li, Steve Finkbeiner, Ernest Fraenkel, Jeffrey Rothstein, Leslie Thompson, Dhruv Sareen, Clive Svendsen, Jennifer E. Van Eyk
Summary: The NIH LINCS program aims to create a publicly available data resource of cell-based biochemical responses or signatures to genetic or environmental perturbations. NeuroLINCS focuses on using hiPSCs to study SMA and ALS, and establishes multi-omic workflows, annotated datasets, and biological pathways. This study focuses on proteomics and the quality of hiPSC lines from 6 individuals, with epigenomics and transcriptomics data also available. The data generated by DIA-MS analysis of the genetically diverse hiPSCs is of high quality and accessible to the public.
Article
Clinical Neurology
Alberto Catanese, Sandeep Rajkumar, Daniel Sommer, Pegah Masrori, Nicole Hersmus, Philip Van Damme, Simon Witzel, Albert Ludolph, Ritchie Ho, Tobias M. Boeckers, Medhanie Mulaw
Summary: Catanese et al. used a multiomics approach to study ALS, identifying a mutation-independent disease signature and providing insights into the convergent pathomechanisms of different mutations. This work contributes to our understanding of ALS by revealing common transcriptional and epigenetic alterations in the disease.
Article
Cell & Tissue Engineering
Alexander H. Laperle, V. Alexandra Moser, Pablo Avalos, Bin Lu, Amanda Wu, Aaron Fulton, Stephany Ramirez, Veronica J. Garcia, Shaughn Bell, Ritchie Ho, George Lawless, Kristina Roxas, Saba Shahin, Oksana Shelest, Soshana Svendsen, Shaomei Wang, Clive N. Svendsen
Summary: This study characterizes iNPC-GDNFs and evaluates their therapeutic potential and safety. The results show that iNPC-GDNFs have neuroprotective effects in models of retinal degeneration and ALS, indicating their potential as a combined cell and gene therapy for various neurodegenerative diseases.
Article
Cell Biology
Dimitrios Tsitsipatis, Krystyna Mazan-Mamczarz, Ying Si, Allison B. Herman, Jen-Hao Yang, Abhishek Guha, Yulan Piao, Jinshui Fan, Jennifer L. Martindale, Rachel Munk, Xiaoling Yang, Supriyo De, Brijesh K. Singh, Ritchie Ho, Myriam Gorospe, Peter H. King
Summary: This study identified differentially abundant circRNAs in ALS-relevant tissues, such as muscle and spinal cord, and revealed the expression patterns of these circRNAs in different stages of the disease. These findings help understand the neuromuscular molecular programs in ALS and could potentially guide the development of therapies.
Article
Computer Science, Interdisciplinary Applications
Divya Ramamoorthy, Kristen Severson, Soumya Ghosh, Karen Sachs, Jonathan D. Glass, Christina N. Fournier, Todd M. Herrington, James D. Berry, Kenney Ng, Ernest Fraenkel
Summary: This study developed an approach based on a mixture of Gaussian processes to identify patterns of disease progression in patients with ALS. The results showed that ALS progression is often nonlinear and can involve periods of stable disease followed by rapid decline. The approach can also be applied to Alzheimer's and Parkinson's diseases.
NATURE COMPUTATIONAL SCIENCE
(2022)