Article
Cell Biology
Takashi Wakui, Mitsuru Negishi, Yuta Murakami, Shunsuke Tominaga, Yasushi Shiraishi, Anne E. Carpenter, Shantanu Singh, Hideo Segawa
Summary: Purification is necessary before differentiating hiPSCs into fully expressing specific differentiation marker genes. The relationship between gene expression levels and cell morphology was investigated using live-cell images and mRNA profiles. A model was built to predict gene expression levels from morphology, achieving similar performance as state-of-the-art methods for predicting gene expression levels from tissue images of cancer genes. This approach provides a practical method for estimating expression levels of a few genes and monitoring the purification process within a reprogramming batch.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Cell & Tissue Engineering
Joonas Sokka, Masahito Yoshihara, Jouni Kvist, Laura Laiho, Andrew Warren, Christian Stadelmann, Eeva-Mari Jouhilahti, Helena Kilpinen, Diego Balboa, Shintaro Katayama, Aija Kyttala, Juha Kere, Timo Otonkoski, Jere Weltner, Ras Trokovic
Summary: Conventional reprogramming methods may lead to heterogeneous reprogramming, while CRISPRa activation can reduce this heterogeneity and achieve high-quality pluripotent reprogramming of human cells.
Review
Endocrinology & Metabolism
Ila Tewari Jasra, Nerea Cuesta-Gomez, Kevin Verhoeff, Braulio A. Marfil-Garza, Nidheesh Dadheech, A. M. James Shapiro
Summary: This review summarizes the roles and mechanisms of mitochondria in somatic cell reprogramming to iPSCs and the metabolic shift associated with directed differentiation into pancreatic beta-like cells.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Deogil Kim, Byung-Hyun Cha, Jinsung Ahn, Yoshie Arai, Bogyu Choi, Soo-Hong Lee
Summary: Understanding the biophysical relationships between stem cells and applied biomaterials is crucial in controlling stem cell functions. This study highlights the significant role of 3D microenvironment, particularly methacrylated hyaluronic acid (HA) hydrogel, in improving cellular reprogramming into iPSCs. The incorporation of cues from the 3D microenvironment accelerates the reprogramming process, offering potential advantages for translational applications.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Cell & Tissue Engineering
Sandhya Sriram, Nam-Young Kang, Subha Subramanian, Tannistha Nandi, Samydurai Sudhagar, Qiaorui Xing, Gerine Jin-Ling Tong, Allen Kuan-Liang Chen, Thekkeparambil Chandrabose Srijaya, Patrick Tan, Yuin-Han Loh, Young-Tae Chang, Shigeki Sugii
Summary: In this study, a novel BODIPY-derived fluorescent probe, BDL-E5, was identified to detect live human iPS cells at the early reprogramming stage, enabling early identification of reprogramming cells and improving the efficiency of iPS cell generation. RNA sequencing analysis revealed early reprogramming gene expression patterns, particularly involving CREB1, which was found to significantly impact reprogramming efficiency when overexpressed or knocked down. Overall, BDL-E5 provides a valuable tool for studying the early reprogramming pathway and enhancing the production of human iPS cells for clinical applications.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Pharmacology & Pharmacy
Lu Zhang, Xiao-Jing-Nan Ma, Yuan-Yuan Fei, Heng-Tong Han, Jun Xu, Lu Cheng, Xun Li
Summary: The liver has the ability to repair itself, but pathological changes can impair its regenerative capacity and lead to liver failure. Mesenchymal stem cells (MSCs) have shown promise in liver regeneration, and induced pluripotent stem cells have made progress in organoid establishment and drug screening.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Doreen Becker, Rosemarie Weikard, Frieder Hadlich, Christa Kuehn
Summary: The analysis of single-cell RNA datasets from bovine milk cells and pbMECs revealed distinct clusters within each population, indicating heterogeneity between the populations. These datasets provide a molecular cell atlas for future studies of milk cell composition and gene expression.
Article
Biotechnology & Applied Microbiology
Viktor Haellman, Pratik Saxena, Yanrui Jiang, Martin Fussenegger
Summary: This study presents a framework for implementing synthetic gene switches in PSCs by combining different elements. By multiplexing the VanA and rtTA systems, independent control of the expression of different transcription factors in human induced PSCs was achieved to enhance lineage specification towards early pancreatic progenitors.
METABOLIC ENGINEERING
(2021)
Article
Genetics & Heredity
Huajin Li, Wenting Xu, Sijia Xiang, Leiting Tao, Wen Fu, Jinhui Liu, Wenbin Liu, Yamei Xiao, Liangyue Peng
Summary: Pluripotency is a transient state in early embryos regulated by a network of pluripotency-related genes. This study identified four pluripotent genes in zebrafish and crucian carp and verified that three of them can be used as markers for pluripotency in induced pluripotent stem cells in fish.
FRONTIERS IN GENETICS
(2022)
Article
Cell & Tissue Engineering
Ana Belen Alvarez-Palomo, Jordi Requena-Osete, Raul Delgado-Morales, Victoria Moreno-Manzano, Carme Grau-Bove, Agueda M. Tejera, Manel Juan Otero, Carme Barrot, Irene Santos-Barriopedro, Alejandro Vaquero, Jovita Mezquita-Pla, Sebastian Moran, Carlos Hobeich Naya, Iris Garcia-Martinez, Francisco Vidal Perez, Maria A. Blasco, Manel Esteller, Michael J. Edel
Summary: The study demonstrates that utilizing synthetic mRNA transfection of CYCLIN D1 during reprogramming repairs DNA and significantly improves the genetic stability of human iPSC. This method reduces various genetic instabilities, decreases DNA damage, promotes correct protein expression, and reduces single-nucleotide polymorphism changes per chromosome.
Article
Hematology
Kai Kammers, Margaret A. Taub, Rasika A. Mathias, Lisa R. Yanek, Kanika Kanchan, Vidya Venkatraman, Niveda Sundararaman, Joshua Martin, Senquan Liu, Dixie Hoyle, Koen Raedschelders, Ronald Holewinski, Sarah Parker, Victoria Dardov, Nauder Faraday, Diane M. Becker, Linzhao Cheng, Zack Z. Wang, Jeffrey T. Leek, Jennifer E. Van Eyk, Lewis C. Becker
Summary: Deriving megakaryocytes (MKs) from pluripotent stem cells (iPSC) allows for the comprehensive study of gene and protein expression important in MK and platelet function. Factors specific to individuals influence the differentiation of MKs from iPSCs, with differential gene and protein expression seen based on subject's sex and race. Numerous genes and proteins highly expressed in MKs provide potential candidates for future research on hematopoiesis, platelet formation, and/or platelet function.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Biology
Wanqiu Chen, Chenguang Wang, Zhi-Xue Yang, Feng Zhang, Wei Wen, Christoph Schaniel, Xianqiang Mi, Matthew Bock, Xiao-Bing Zhang, Hongyu Qiu, Charles Wang
Summary: Researchers have developed a method to generate induced mesenchymal stromal cells (iMSCs) by directly reprogramming human peripheral blood mononuclear cells (PBMCs) using five factors. Omission of OCT4, one of the factors, significantly impairs the functionality of iMSCs and downregulates MSC-specific and mesoderm-regulating genes. The transient expression of OCT4 increases chromatin accessibility and promotes demethylation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Parvin Forghani, Aysha Rashid, Fangxu Sun, Rui Liu, Dong Li, Megan R. Lee, Hyun Hwang, Joshua T. Maxwell, Anant Mandawat, Ronghu Wu, Khalid Salaita, Chunhui Xu
Summary: Anti-cancer therapies have improved patient outcomes, but cardiac side effects from these treatments are still a significant challenge. This study investigated the mechanisms underlying cardiotoxicity induced by the proteasome inhibitor carfilzomib using hiPSC-CMs. The findings showed that carfilzomib treatment caused deleterious changes in cellular and functional characteristics of hiPSC-CMs, affecting mitochondrial function and contractility. Insights into these changes were gained from omic analyses of gene and protein expression.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Review
Immunology
Niclas Flosdorf, Martin Zenke
Summary: Novel methods of generating dendritic cells (DC) through reprogramming somatic cells have opened up exciting avenues for research and clinical applications. Induced pluripotent stem cells (iPS cells) and direct reprogramming of cells can both be used to generate DC.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Amanda J. Collier, Adam Bendall, Charlene Fabian, Andrew A. Malcolm, Katarzyna Tilgner, Claudia Semprich, Katarzyna Wojdyla, Paola Serena Nisi, Kamal Kishore, Valar Nila Roamio Franklin, Bahar Mirshekar-Syahkal, Clive D'Santos, Kathrin Plath, Kosuke Yusa, Peter J. Rugg-Gunn
Summary: Identifying essential regulators and major impediments of human primed to naive pluripotent stem cell reprogramming through genome-wide screening, it was discovered that factors crucial for cell state change are typically repurposed with new functions rather than undergoing changes at the gene expression level. In addition, small-molecule inhibitors of reprogramming impediments were found to enhance naive cell reprogramming beyond current methods. This work not only defines principles controlling the establishment of human naive pluripotency, but also provides new insights into mechanisms destabilizing and reconfiguring cell identity during cell state transitions.
Article
Veterinary Sciences
Liliana Endo-Munoz, Tristram C. Bennett, Eleni Topkas, Sherry Y. Wu, Douglas H. Thamm, Laura Brockley, Maureen Cooper, Scott Sommerville, Maurine Thomson, Kathleen O'Connell, Amy Lane, Guy Bird, Anne Peaston, Nicholas Matigian, Rodney C. Straw, Nicholas A. Saunders
VETERINARY AND COMPARATIVE ONCOLOGY
(2020)
Article
Neurosciences
Maria A. Kasherman, Susitha Premarathne, Thomas H. J. Burne, Stephen A. Wood, Michael Piper
MOLECULAR NEUROBIOLOGY
(2020)
Article
Oncology
Sandra Pavey, Alex Pinder, Winnie Fernando, Nicholas D'Arcy, Nicholas Matigian, Dubravka Skalamera, Kim-Anh Le Cao, Dorothy Loo-Oey, Michelle M. Hill, Mitchell Stark, Michael Kimlin, Andrew Burgess, Nicole Cloonan, Richard A. Sturm, Brian Gabrielli
MOLECULAR ONCOLOGY
(2020)
Article
Multidisciplinary Sciences
Nick R. Glass, Minoru Takasako, Pei Xuan Er, Drew M. Titmarsh, Alejandro Hidalgo, Ernst J. Wolvetang, Melissa H. Little, Justin J. Cooper-White
Article
Plant Sciences
Dongdong Wang, Mariyam Murtaza, Stephen A. Wood, George D. Mellick, William Gang Miao, Gordon P. Guymer, Paul Forster, Yunjiang Feng, Ronald J. Quinn
JOURNAL OF NATURAL PRODUCTS
(2020)
Editorial Material
Ethics
Rachel A. Ankeny, Ernst Wolvetang
AMERICAN JOURNAL OF BIOETHICS
(2021)
Article
Multidisciplinary Sciences
Uddalak Majumdar, Sathiyanarayanan Manivannan, Madhumita Basu, Yukie Ueyama, Mark C. Blaser, Emily Cameron, Michael R. McDermott, Joy Lincoln, Susan E. Cole, Stephen Wood, Elena Aikawa, Brenda Lilly, Vidu Garg
Summary: Nitric oxide regulates NOTCH pathway through S-nitrosylation to prevent calcific aortic valve disease.
Review
Neurosciences
Alan Mackay-Sim
Summary: Hereditary spastic paraplegia (HSP) is a genetically diverse group of disorders affecting upper motor neurons, with 80 genes or genomic loci associated with the diagnosis. Treatments for HSP are challenging due to the rare disease's genetic heterogeneity, but identifying disease-associated cell dysfunctions may lead to potential drug targets.
Article
Cell Biology
Julio Aguado, Harman K. Chaggar, Cecilia Gomez-Inclan, Mohammed R. Shaker, Hannah C. Leeson, Alan Mackay-Sim, Ernst J. Wolvetang
Summary: Ataxia-telangiectasia (A-T) is a genetic disorder caused by the lack of functional ATM kinase, leading to chronic inflammation and premature aging in the central nervous system. The cGAS-STING pathway is shown to play a crucial role in recognizing micronuclei and inducing senescence-associated secretory phenotype (SASP) in A-T cells and brain organoids, making it a novel therapeutic target for treating neuropathology in A-T patients.
Article
Cell Biology
Riikka Lampinen, Mohammad Feroze Fazaludeen, Simone Avesani, Tiit Ord, Elina Penttila, Juha-Matti Lehtola, Toni Saari, Sanna Hannonen, Liudmila Saveleva, Emma Kaartinen, Francisco Fernandez Acosta, Marcela Cruz-Haces, Heikki Lopponen, Alan Mackay-Sim, Minna U. Kaikkonen, Anne M. Koivisto, Tarja Malm, Anthony R. White, Rosalba Giugno, Sweelin Chew, Katja M. Kanninen
Summary: This study evaluated the differences in olfactory mucosa between cognitively healthy individuals and Alzheimer's disease patients. The findings showed increased secretion of amyloid-beta in Alzheimer's disease olfactory mucosal cells and identified 240 differentially expressed disease-associated genes and five distinct cell populations. The study also revealed alterations in RNA and protein metabolism, inflammatory processes, and signal transduction in multiple cell populations, suggesting their involvement in Alzheimer's disease-related olfactory mucosa pathophysiology. Additionally, the study proposed alterations in gene expression of mitochondrially located genes in AD OM cells, which were verified by functional assays, demonstrating altered mitochondrial respiration and a reduction of ATP production. The results highlight the changes in olfactory mucosal cells in Alzheimer's disease and demonstrate the significance of single-cell RNA sequencing data in investigating the molecular and cellular mechanisms associated with the disease.
Article
Biochemical Research Methods
Stephen A. Wood, Peter G. Hains, Arnaud Muller, Melissa Hill, Susitha Premarathne, Mariyam Murtaza, Phillip J. Robinson, George D. Mellick, Alex M. Sykes
Summary: In this study, we quantified proteomic differences between healthy control and PD patient cells and identified the critical role of the unfolded protein response (UPR) in PD patients. PD patients with high amounts of PDIA6 and HYOU1 proteins were more sensitive to endoplasmic reticulum stress. These findings provide insight into underlying cellular dysfunctions in PD patients.
PROTEOMICS CLINICAL APPLICATIONS
(2022)
Article
Biochemistry & Molecular Biology
William Gang Miao, Thanh Nguyen, Jamila Iqbal, Gregory K. Pierens, Linlin Ma, Des R. Richardson, Stephen A. Wood, George D. Mellick, Ronald J. Quinn, Yunjiang Feng
Summary: This study evaluated the effects of natural compounds from Ligusticum chuanxiong on Parkinson's Disease (PD) cells, and found that 34 compounds strongly affected the staining of multiple cellular organelles, which are closely related to the pathogenesis of PD. The results helped rationalize the traditional use of Ligusticum chuanxiong in PD treatment, and these compounds can serve as chemical probes to study the molecular pathways of PD.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Engineering, Environmental
Md Hafiz All Hosen, Alex M. M. Sykes, Stephen A. A. Wood, Frederic D. L. Leusch, Deanne J. J. Whitworth, Susan M. Bengtson M. Nash
Summary: Cetaceans are at risk of accumulating environmental contaminants due to their longevity and high body fat. However, there is a lack of specific chemical effect data for these species. Recent advances in cetacean cell culture have allowed for the application of toxicological effect assessment approaches.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Biology
Louisa C. E. Windus, Nicholas Matigian, Vicky M. M. Avery
Summary: This study aimed to establish a biologically relevant 3D in vitro model that mimics the cellular and molecular profiles of metastasis-associated fibroblasts (MAFs) found in vivo. Using 3D in vitro cell culture models, the bone-derived fibroblast cell line, HS-5, was treated with conditioned media from metastatic-derived prostate cancer cell lines, PC3 and MDA-PCa 2b, or mouse-derived fibroblasts 3T3. The resulting HS5-PC3 and HS5-MDA cell lines displayed alterations in expression levels and genomic profiles consistent with subpopulations of MAFs reported in vivo. The use of these engineered 3D models could provide insights into the novel biology regulating metastatic growth and the role of fibroblasts in the colonization process.
Article
Geriatrics & Gerontology
Mohammed R. Shaker, Julio Aguado, Harman Kaur Chaggar, Ernst J. Wolvetang
Summary: The study reveals an important role for the Klotho protein in regulating human neuronal senescence, with moderate regulation of KL expression affecting the aging process of cells. Furthermore, KL may act in a paracrine fashion to inhibit neuronal senescence.
NPJ AGING AND MECHANISMS OF DISEASE
(2021)