Article
Cell Biology
Yiran Meng, Joana Carrelha, Roy Drissen, Xiying Ren, Bowen Zhang, Adriana Gambardella, Simona Valletta, Supat Thongjuea, Sten Eirik Jacobsen, Claus Nerlov
Summary: The lymphoid fate in haematopoietic stem cells is determined through epigenetic programming rather than transcriptional control, which also influences the differentiation pathways of platelets with distinct kinetics.
NATURE CELL BIOLOGY
(2023)
Article
Biology
Michael Borg, Ranjith K. Papareddy, Rodolphe Dombey, Elin Axelsson, Michael D. Nodine, David Twell, Frederic Berger
Summary: The alternation between morphologically distinct haploid and diploid life forms in plants and algae is controlled by epigenetic modifications such as the loss of H3K9me2 and global loss of H3K27me3. These events lead to significant changes in chromatin accessibility and transcriptional reprogramming, guiding the transition between generations in flowering plants.
Article
Immunology
Sloan A. Lewis, Suhas Sureshchandra, Brianna Doratt, Vanessa A. Jimenez, Cara Stull, Kathleen A. Grant, Ilhem Messaoudi
Summary: Chronic heavy drinking can alter classical monocyte subset composition, leading to a hyper-inflammatory response to LPS but a compromised response to pathogens. This dysregulated inflammatory response may increase susceptibility to infections and impair wound healing.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell & Tissue Engineering
Xinhui Liu, Aamir Khan, Huan Li, Shensen Wang, Xuechai Chen, Hua Huang
Summary: Emerging evidence suggests that vitamin C enhances the reprogramming process by acting as a cofactor in DNA and histone demethylation. It also potentially plays a role in regulating RNA methylation and cellular reprogramming. This review highlights the significance of vitamin C in epigenetic regulation and its affiliation with demethylases in facilitating epigenetic reprogramming.
CURRENT STEM CELL RESEARCH & THERAPY
(2022)
Article
Multidisciplinary Sciences
Xiaoyu Tracy Cai, Hongjie Li, Martin Borch Jensen, Elie Maksoud, Jovencio Borneo, Yuxin Liang, Stephen R. Quake, Liqun Luo, Pejmun Haghighi, Heinrich Jasper
Summary: Glial metabolic reprogramming by gut-derived cytokines in Drosophila results in lasting changes in the sensory system of an ageing organism. This metabolic reprogramming is transient in young flies but becomes constitutive in old flies, contributing to an age-related decline in sensory discrimination.
Article
Urology & Nephrology
Zihui Yu, Ziying Xu, Yuan Liang, Pengbin Yin, Yue Shi, Jiayi Yu, Junfeng Hao, Ting Wang, Weimin Ci
Summary: This study reveals the role of vitamin C in renal homeostasis and pathogenesis, suggesting that vitamin supplementation may be a preventive approach to reduce the risk of kidney injury.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Review
Cell Biology
Adele Alagia, Monika Gullerova
Summary: The dynamics of DNA and RNA methylation are closely related to cellular processes such as development, differentiation, and genome integrity. Dysregulation of methyltransferases and demethylase enzymes has been associated with genome instability and cancer progression. Additionally, post-transcriptional DNA/RNA modifications play important roles in cellular function and the response to environmental cues. m(5)C, a key modification, has been identified as a regulator of the DNA damage response, although its mechanisms of deposition and removal and its role within the cell are still not fully understood.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aiwen Jiang, Yangyang Ma, Xue Zhang, Qianqian Pan, Pengfei Luo, Hongyun Guo, Wangjun Wu, Juan Li, Tong Yu, Honglin Liu
Summary: This study investigates the aberrant epigenetic reprogramming during the formation of piPSCs in pigs. It reveals that incomplete chromatin remodeling and DNA demethylation hinder pluripotent activation, resulting in low expression of endogenous pluripotency genes. The study also highlights the abnormal expression of potential imprinted genes in piPSCs, providing insight into porcine-iPSC reprogramming and genome imprinting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mohsen Afarideh, Roman Thaler, Farzaneh Khani, Hui Tang, Kyra L. Jordan, Sabena M. Conley, Ishran M. Saadiq, Yasin Obeidat, Aditya S. Pawar, Alfonso Eirin, Xiang-Yang Zhu, Amir Lerman, Andre J. van Wijnen, Lilach O. Lerman
Summary: Obesity induces global genomic epigenetic alterations in swine MSCs, primarily involving reduced levels of DNA hydroxymethylation and histone tri-methylation, which are associated with MSC function and clinical features of obesity. Co-incubation with vitamin C enhances some epigenetic marks in obese MSCs, suggesting potential therapeutic targets for obesity.
Article
Pharmacology & Pharmacy
Marius Kreiss, Julia H. Oberlis, Sabine Seuter, Iris Bischoff-Kont, Duran Sueruen, Dominique Thomas, Tamara Goebel, Tobias Schmid, Olof Radmark, Ralf P. Brandes, Robert Fuerst, Ann-Kathrin Haefner, Dieter Steinhilber
Summary: This study reveals a noncanonical function of 5-LO as a transcriptional regulator in monocytic cells. Through gene knockout and RNA-Seq analysis, the study identifies 5-LO regulated genes and shows its effects on cell adhesion and tryptophan metabolism.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pere Llinas-Arias, Miquel Ensenyat-Mendez, Sandra Iniguez-Munoz, Javier I. J. Orozco, Betsy Valdez, Matthew P. Salomon, Chikako Matsuba, Maria Solivellas-Pieras, Andres F. Bedoya-Lopez, Borja Sese, Anja Mezger, Mattias Ormestad, Fernando Unzueta, Siri H. Strand, Alexander D. Boiko, E. Shelley Hwang, Javier Cortes, Maggie L. Dinome, Manel Esteller, Mathieu Lupien, Diego M. Marzese
Summary: Our study reveals the clinical relevance of an insulator element near the MMP8 gene in TNBC patients, which affects MMP gene expression and invasive ability. Disruption of this element changes the MMP expression pattern, influencing tumor cell invasion.
Article
Biotechnology & Applied Microbiology
Cierra J. Walker, Dilara Batan, Carrie T. Bishop, Daniel Ramirez, Brian A. Aguado, Megan E. Schroeder, Claudia Crocini, Jessica Schwisow, Karen Moulton, Laura Macdougall, Robert M. Weiss, Mary A. Allen, Robin Dowell, Leslie A. Leinwand, Kristi S. Anseth
Summary: Aortic valve stenosis (AVS) is a fibrotic disease characterized by thickened valve leaflets. The activation of valve interstitial cells (VICs) to myofibroblasts (aVICs) plays a crucial role in AVS. This study reveals the importance of epigenetic mechanisms and mechanical regulation in VIC activation, and identifies CREBBP as a potential therapeutic target for AVS.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Ana P. Kutschat, Feda H. Hamdan, Xin Wang, Alexander Q. Wixom, Zeynab Najafova, Christine S. Gibhardt, Waltraut Kopp, Jochen Gaedcke, Philipp Strobel, Volker Ellenrieder, Ivan Bogeski, Elisabeth Hessmann, Steven A. Johnsen
Summary: Gemcitabine-resistant PDAC tumors show coamplification of RRM1 and STIM1, where RRM1 is required for resistance while high STIM1 levels lead to increased cytosolic calcium levels. This calcium influx impairs ER stress response and activates NFAT signaling, revealing a potential target for therapy in PDAC.
Article
Marine & Freshwater Biology
Beh Reh, Xuegeng Wang, Yashi Feng, Ramji K. Bhandari
Summary: Perchlorate, a chemical compound commonly used in military artillery and equipment, has been found in various environmental sources. This study investigated the effects of perchlorate exposure on medaka embryonic development and primordial germ cells (PGCs) migration. The results showed that perchlorate exposure delayed hatching time, reduced heartbeat, inhibited PGCs migration, and increased developmental abnormalities. Vitamin C co-treatment alleviated perchlorate-induced embryo mortality. Furthermore, perchlorate altered the global transcriptional network in PGCs, suggesting its potential effects on developing germ cells and fertility.
AQUATIC TOXICOLOGY
(2022)
Article
Genetics & Heredity
Jared A. Tangeman, Agustin Luz-Madrigal, Sutharzan Sreeskandarajan, Erika Grajales-Esquivel, Lin Liu, Chun Liang, Panagiotis A. Tsonis, Katia Del Rio-Tsonis
Summary: This study explored the mechanisms of embryonic RPE reprogramming through RNA-seq analysis, revealing that FGF2 and the MAPK cascade are crucial drivers. Key processes involved cell cycle progression, injury response, migration, and ECM regulation, highlighting the important roles of ECM and EMT dynamics in the reprogramming process.
Article
Ophthalmology
Jonathan F. Russell, Victor M. Villegas, Stephen G. Schwartz, Christina Y. Weng, Janet L. Davis, Harry W. Flynn, J. William Harbour
Summary: The study examined 12 patients diagnosed with exophytic JRCH at Bascom Palmer Eye Institute and Baylor College of Medicine. Multimodal imaging is valuable in the diagnosis of JRCH, aiding in ruling out other conditions.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Biology
Stefan Kurtenbach, James J. Dollar, Anthony M. Cruz, Michael A. Durante, Christina L. Decatur, J. William Harbour
Summary: Single-cell RNA sequencing (scRNA-seq) is a transformative technology that is visualized using dimensional reduction techniques like UMAP and tSNE. PieParty enhances this visualization by representing each cell as a pie chart with slices corresponding to gene expression, allowing for the simultaneous visualization of multiple genes and gene networks in an information-dense and intuitive manner.
LIFE SCIENCE ALLIANCE
(2021)
Article
Oncology
J. William Harbour
Summary: Through a synthetic lethal screen, ERK activation was found to mediate resistance to FAK inhibition in GNAQ-mutant uveal melanoma. Combining inhibition of PLCB-PKC-ERK and Trio-FAK-Yap, representing compensatory effectors of mutant Gaq signaling, may be a promising therapeutic strategy in metastatic uveal melanoma.
CLINICAL CANCER RESEARCH
(2021)
Article
Ophthalmology
Sushant Wagley, Peter J. Belin, James J. Dollar, J. William Harbour, Amanda C. Maltry, Prithvi Mruthyunjaya, A. M. Y. C. Schefler, Peter H. Tang
Summary: Unilateral multifocal uveal melanomas in the setting of ocular melanosis may result from the development of genetically independent primary tumors, as indicated by the mutation profiles of each tumor.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Oncology
Vivian Chua, Anna Han, Nelisa Bechtel, Timothy J. Purwin, Emily Hunter, Connie Liao, J. William Harbour, Andrew E. Aplin
Summary: Metastatic uveal melanoma with BAP1 alterations show elevated AMPK pathway activation, suggesting a potential therapeutic target. Re-expression of BAP1 reduces phosphorylation levels of AMPK and ACC. The survival function of AMPK in BAP1 mutant UM cells is mediated by CaMKK2 and LKB1.
PIGMENT CELL & MELANOMA RESEARCH
(2022)
Article
Oncology
Usman Baqai, Timothy J. Purwin, Nelisa Bechtel, Vivian Chua, Anna Han, Edward J. Hartsough, Jeffim N. Kuznetsoff, J. William Harbour, Andrew E. Aplin
Summary: This study demonstrates that loss of BAP1 in uveal melanoma leads to upregulation of cell adhesion molecules (CAMs), including E-cadherin, CADM1, and SDC2. The reexpression of BAP1 reduces the levels of these molecules and functional experiments show that knockdown of E-cadherin and CADM1 affects spheroid cluster formation and cell growth, respectively.
MOLECULAR CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Antoine J. Ribieras, Yulexi Y. Ortiz, Sophie Shrestha, C. Theodore Huerta, Hongwei Shao, Maria E. Boulina, Roberto Vazquez-Padron, Zhao-Jun Liu, Omaida C. Velazquez
Summary: Peripheral arterial disease (PAD) is a significant disease resulting from atherosclerotic risk factors. This study focuses on a unique method to induce footpad gangrene in mice that resembles chronic limb-threatening ischemia (CLTI), which is the most severe form of PAD. The method combines femoral artery and vein electrocoagulation with the administration of a nitric oxide synthase (NOS) inhibitor. The study also introduces a novel approach using intracardiac perfusion and whole-mount confocal laser scanning microscopy to assess reperfusion.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Cardiac & Cardiovascular Systems
Antoine J. Ribieras, Yulexi Y. Ortiz, Yan Li, Carlos T. Huerta, Nga Le, Hongwei Shao, Roberto I. Vazquez-Padron, Zhao-Jun Liu, Omaida C. Velazquez
Summary: In patients with chronic limb-threatening ischemia and limited revascularization options, gene therapy using E-selectin/AAV2/2 shows promise in improving limb perfusion and function by reducing gangrene severity and enhancing angiogenesis and endothelial progenitor cell recruitment.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Matthew G. Field, Jeffim N. Kuznetsoff, Michelle G. Zhang, James J. Dollar, Michael A. Durante, Yoseph Sayegh, Christina L. Decatur, Stefan Kurtenbach, Daniel Pelaez, J. William Harbour
Summary: This study identifies a previously unknown dependency of Rb cells on ESRRG and implicates ESRRG as a potential therapeutic target in Rb.
Article
Oncology
Michelle G. Zhang, Jeffim N. Kuznetsoff, Dawn A. Owens, Ryan A. Gallo, Karthik Kalahasty, Anthony M. Cruz, Stefan Kurtenbach, Zelia M. Correa, Daniel Pelaez, J. William Harbour
Summary: Despite advances in chemotherapy, chemoresistance continues to be a major issue in retinoblastoma. The study showed that carboplatin induced molecular reprogramming, upregulating targets in the PI3K-AKT pathway, including ABC transporters and metabolic regulators. These targets could be potentially inhibited to overcome chemoresistance.
Article
Dermatology
Carlos Theodore Huerta, Yulexi Y. Ortiz, Zhao-Jun Liu, Omaida C. Velazquez
Summary: Given their capacity for self-renewal, multilineage differentiation, and immunomodulatory potential, mesenchymal stem cells (MSCs) represent a promising modality of clinical therapy for both regenerative medicine and immune diseases. In this study, we review the key approaches and popular methods utilized to boost potency and modify functions of MSCs for clinical purposes as well as their associated limitations.
ADVANCES IN WOUND CARE
(2023)
Review
Cardiac & Cardiovascular Systems
Carlos Theodore Huerta, Francesca A. Voza, Yulexi Y. Ortiz, Zhao-Jun Liu, Omaida C. Velazquez
Summary: Progressive peripheral arterial disease (PAD) can lead to chronic limb-threatening ischemia (CLTI), resulting in non-healing wounds and tissue loss. Current therapies for CLTI, such as revascularization and medical management, have limitations, and regenerative therapies utilizing mesenchymal stem/stromal cells (MSCs) hold promise in improving wound healing and limb salvage. In this review, we focus on the specific effects of MSC-based therapeutics on ischemic non-healing wounds associated with CLTI, providing insights from pre-clinical and clinical studies.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Antoine J. Ribieras, Yulexi Y. Ortiz, Yan Li, Nga T. Le, Carlos T. Huerta, Francesca A. Voza, Hongwei Shao, Roberto I. Vazquez-Padron, Zhao-Jun Liu, Omaida C. Velazquez
Summary: This study evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. The results showed that mice treated with E-selectin gene therapy had improved hindlimb perfusion, exercise capacity, and enhanced regeneration of ischemic skeletal muscle. These findings suggest a potential role for E-selectin gene therapy as a nonsurgical adjunct in patients with peripheral artery disease.
CARDIOVASCULAR THERAPEUTICS
(2023)
Article
Oncology
Anna Han, Dzmitry Mukha, Vivian Chua, Timothy J. Purwin, Manoela Tiago, Bhavik Modasia, Usman Baqai, Jenna L. Aumiller, Nelisa Bechtel, Emily Hunter, Meggie Danielson, Mizue Terai, Philip B. Wedegaertner, Takami Sato, Solange Landreville, Michael A. Davies, Stefan Kurtenbach, J. William Harbour, Zachary T. Schug, Andrew E. Aplin
Summary: Metastatic uveal melanoma is difficult to treat, but targeting metabolic pathways, such as lipid/fat metabolism and mTOR, may be a potential therapeutic approach. The upregulation of enzymes involved in lipid/fat metabolism, such as FASN, and activation of the mTOR pathway were observed in uveal melanoma cells. Inhibiting FASN and mTOR led to the suppression of uveal melanoma cell growth, suggesting a novel treatment strategy for uveal melanoma.