Article
Biochemistry & Molecular Biology
Zeba Sultana, Mathurin Dorel, Bertram Klinger, Anja Sieber, Ilona Dunkel, Nils Bluethgen, Edda G. Schulz
Summary: By combining systematic perturbation experiments with mathematical modeling, it was found that the number of active X chromosomes in mouse embryonic stem cells affects cell signaling and differentiation propensity. The presence of a single active X chromosome makes cells more sensitive to differentiation-promoting pathways and leads to a stronger negative feedback in the MAPK pathway. This may explain the delayed differentiation observed in female mouse embryonic stem cells.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yuka Tamura, Tatsuya Ohhata, Hiroyuki Niida, Satoshi Sakai, Chiharu Uchida, Kazuma Masumoto, Fuminori Katou, Anton Wutz, Masatoshi Kitagawa
Summary: The study reveals that female ESCs are more sensitive to camptothecin and have lower gene targeting efficiency than male ESCs, indicating reduced homologous recombination efficiency in female ESCs. Lower HR efficiency is restored when X chromosome inactivation is induced. X-linked gene Brcc3 is involved in promoting proper HR.
Article
Biochemistry & Molecular Biology
Yuka Sakata, Hong Zhang, Akiko Sugiyama, Nami Motosugi, Hiroshi Kimura, Yosuke Okamura, Atsushi Fukuda
Summary: High-resolution imaging analysis is essential for studying cell functions, but culturing cells on glass substrates often leads to cell instability. In this study, we coated the glass substrate with a nanosheet composed of hydrophobic polystyrene and Matrigel, which significantly improved the viability of human pluripotent stem cells (hPSCs). The nanosheet coating did not affect the transcriptome status of hPSC and allowed for high-resolution imaging assay. Our findings demonstrate that the nanosheet coating is beneficial for sensitive cells cultured on glass substrates.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
Roni Sarel-Gallily, Nissim Benvenisty
Summary: This study investigates the changes in the status of the X chromosome between primed and naive human embryonic stem cells (hESCs). The findings suggest that naive hESCs reactivate XIST gene and show increased gene expression levels on the X chromosome. However, the reactivation of the X chromosome in naive hESCs is not uniform and presents a distinct eroded pattern.
Article
Biochemistry & Molecular Biology
Matthew M. Edwards, Michael Zuccaro, Ido Sagi, Qiliang Ding, Dan Vershkov, Nissim Benvenisty, Dieter Egli, Amnon Koren
Summary: The study found differences in DNA replication timing between haploid human embryonic stem cells and diploid cells, with unique features of delayed replication in certain genomic regions, especially the X Chromosome. The dosage effect of active X Chromosomes may affect the speed of chromosomal replication.
Article
Cell & Tissue Engineering
Ani Grigoryan, Johannes Pospiech, Stephen Kramer, Daniel Lipka, Thomas Liehr, Hartmut Geiger, Hiroshi Kimura, Medhanie A. Mulaw, Maria Carolina Florian
Summary: The study demonstrates the important role of LaminA/C in establishing a repressive compartment for XCI in young HSCs, which becomes impaired in aged HSCs, leading to dysregulation of XCI.
Article
Multidisciplinary Sciences
Darcy T. Ahern, Prakhar Bansal, Maria K. Armillei, Isaac V. Faustino, Yuvabharath Kondaveeti, Heather R. Glatt-Deeley, Erin C. Banda, Stefan F. Pinter
Summary: This study investigates the impact of monosomy X on syncytiotrophoblast development in humans using X-monosomic human induced pluripotent stem cells (hiPSCs). The results suggest that monosomy X may alter the levels of placental genes and secretion of placental growth factor (PlGF) and human chorionic gonadotropin (hCG). The findings also demonstrate that the corresponding gene coexpression network modules are preserved in chorionic villi and term placenta.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Shogo Matoba, Chisayo Kozuka, Kento Miura, Kimiko Inoue, Mami Kumon, Ryoya Hayashi, Tatsuya Ohhata, Atsuo Ogura, Azusa Inoue
Summary: Genomic imprinting regulates monoallelic gene expression dependent on parental origin. The LOI of noncanonical imprinted gene Xist, which causes aberrant transient maternal X-chromosome inactivation (XCI) at preimplantation, greatly affects the development of Eed matKO embryos. Noncanonical imprinting also restrains placental overgrowth.
GENES & DEVELOPMENT
(2022)
Article
Cell Biology
Yolanda W. Chang, Arend W. Overeem, Celine M. Roelse, Xueying Fan, Christian Freund, Susana M. Chuva de Sousa Lopes
Summary: The study investigated whether differences in X chromosome inactivation in female hPSCs could affect the variability in hPGCLC differentiation efficiency. Results showed that XCI state did not directly impact differentiation efficiency, but rather depended on the cell source. Regardless of the XCI state of hPSCs, both hPGCLCs and soma cells in EBs exhibited signs of X chromosome inactivation.
Article
Multidisciplinary Sciences
Narendra Kumar Chunduri, Paul Menges, Xiaoxiao Zhang, Angela Wieland, Vincent Leon Gotsmann, Balca R. Mardin, Christopher Buccitelli, Jan O. Korbel, Felix Willmund, Maik Kschischo, Markus Raeschle, Zuzana Storchova
Summary: Chromosome loss leading to monosomy is detrimental to cell viability, affecting proliferation and genomic stability. The study found that genes encoded on the lost chromosomes were downregulated, leading to defects in protein synthesis and ribosome assembly. The incompatibility of monosomy with p53 expression is associated with impaired ribosome biogenesis and contributes to monosomy in cancer.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Sarah Pyfrom, Bam Paneru, James J. Knox, Michael P. Cancro, Sylvia Posso, Jane H. Buckner, Montserrat C. Anguera
Summary: SLE, a female-predominant autoimmune disease, is associated with X-linked gene inactivation and abnormal X chromosome inactivation in B cells. Researchers found that aberrant maintenance of X chromosome inactivation in B cells is a feature of SLE, leading to abnormal X-linked gene expression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Developmental Biology
Andrew Keniry, Natasha Jansz, Peter F. Hickey, Kelsey A. Breslin, Megan Iminitoff, Tamara Beck, Quentin Gouil, Matthew E. Ritchie, Marnie E. Blewitt
Summary: Female mouse embryonic stem cells (mESCs) present differently from male mESCs due to the transcriptional activity of the second X chromosome. To study female pluripotency effectively, high-quality cultures of XX female mESCs are crucial.
Article
Cell & Tissue Engineering
Rowan M. Karvas, Shafqat A. Khan, Sonam Verma, Yan Yin, Devesha Kulkarni, Chen Dong, Kyoung-mi Park, Brian Chew, Eshan Shane, Laura A. Fischer, Deepak Kumar, Liang Ma, Adrianus C. M. Boon, Sabine Dietmann, Indira U. Mysorekar, Thorold W. Theunissen
Summary: This study reports the formation of 3D trophoblast organoids derived from naive human pluripotent stem cells. These organoids exhibit a villous architecture similar to primary trophoblast organoids and display distinct trophoblast cell types. Importantly, they also show selective vulnerability to emerging pathogens such as SARS-CoV-2 and Zika virus. This research provides an accessible model system for studying placental development and its susceptibility to emerging pathogens.
Article
Multidisciplinary Sciences
Francisco Bustos, Carmen Espejo-Serrano, Anna Segarra-Fas, Rachel Toth, Alison J. Eaton, Kristin D. Kernohan, Meredith J. Wilson, Lisa G. Riley, Greg M. Findlay
Summary: TOKAS is an X-linked intellectual disability syndrome caused by variants in the gene encoding RLIM. A novel missense variant in RLIM disrupts protein expression and function, leading to a severe form of the syndrome. This variant impairs E3 ubiquitin ligase activity and disrupts X-chromosome inactivation.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Siyuan Liu, Nirmala Akula, Paul K. Reardon, Jill Russ, Erin Torres, Liv S. Clasen, Jonathan Blumenthal, Francois Lalonde, Francis J. McMahon, Francis Szele, Christine M. Disteche, M. Zameel Cader, Armin Raznahan
Summary: This study investigates the effects of X, Y, and 21 aneuploidies on gene expression in lymphoblastoid cell lines, fibroblasts, and iPSC-derived neuronal cells. It confirms theoretical models of sex chromosome dosages sensitivity and identifies a set of 41 genes that show obligate dosage sensitivity. The study finds that cis effects of sex chromosome dosages are preserved in different cell types, while trans effects are mostly not preserved.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Endocrinology & Metabolism
Paula B. T. Fettback, Ricardo M. A. Pereira, Andre M. Rocha, Jose Maria Soares-, Gary D. Smith, Edmund C. Baracat, Paulo C. Serafini
GYNECOLOGICAL ENDOCRINOLOGY
(2016)
Article
Cardiac & Cardiovascular Systems
Todd J. Herron, Andre Monteiro Da Rocha, Katherine F. Campbell, Daniela Ponce-Balbuena, B. Cicero Willis, Guadalupe Guerrero-Serna, Qinghua Liu, Matt Klos, Hassan Musa, Manuel Zarzoso, Alexandra Bizy, Jamie Furness, Justus Anumonwo, Sergey Mironov, Jose Jalife
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2016)
Article
Cardiac & Cardiovascular Systems
Michael Balistreri, Justin A. Davis, Katherine F. Campbell, Andre Monteiro da Rocha, Marjorie C. Treadwell, Todd J. Herron
PEDIATRIC CARDIOLOGY
(2017)
Article
Multidisciplinary Sciences
Andre Monteiro da Rocha, Katherine Campbell, Sergey Mironov, Jiang Jiang, Lakshmi Mundada, Guadalupe Guerrero-Serna, Jose Jalife, Todd J. Herron
SCIENTIFIC REPORTS
(2017)
Article
Neurosciences
Jill M. Haenfler, Geena Skariah, Caitlin M. Rodriguez, Andre Monteiro da Rocha, Jack M. Parent, Gary D. Smith, Peter K. Todd
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2018)
Article
Cardiac & Cardiovascular Systems
Alvaro Macias, J. Jaime Diaz-Larrosa, Yaazan Blanco, Victor Fanjul, Cristina Gonzalez-Gomez, Pilar Gonzalo, Maria Jesus Andres-Manzano, Andre Monteiro da Rocha, Daniela Ponce-Balbuena, Andrew Allan, David Filgueiras-Rama, Jose Jalife, Vicente Andres
Summary: This study found that heart tissue from Hutchinson-Gilford progeria syndrome (HGPS) patients has structural and electrophysiological defects, including disruption of the t-tubular system, shortened sarcomeres, bradycardia, and atrio-ventricular conduction abnormalities. Chronic treatment with low-dose paclitaxel partially corrected these abnormalities.
CARDIOVASCULAR RESEARCH
(2022)
Article
Endocrinology & Metabolism
Abdelwahab Jalal Eldin, Baris Akinci, Andre Monteiro da Rocha, Rasimcan Meral, Ilgin Yildirim Simsir, Suleyman Cem Adiyaman, Ebru Ozpelit, Nicole Bhave, Ramazan Gen, Banu Yurekli, Nilufer Ozdemir Kutbay, Zeynep Siklar, Adam H. Neidert, Rita Hench, Marwan K. Tayeh, Jeffrey W. Innis, Jose Jalife, Hakan Oral, Elif A. Oral
Summary: LMNA variants are associated with a higher prevalence of cardiac events, particularly arrhythmias, in patients with familial partial lipodystrophy (FPLD). Non-codon 482 LMNA variants are more likely to be associated with cardiac events, especially atrial fibrillation or flutter. Studies on LMNA mutant hiPSC-CMs show increased spontaneous activity and shorter action potential duration.
CLINICAL ENDOCRINOLOGY
(2021)
Article
Medicine, Research & Experimental
Justin Davis, Ahmad Chouman, Jeffery Creech, Andre Monteiro da Rocha, Daniela Ponce-Balbuena, Eric N. Jimenez Vazquez, Ruthann Nichols, Andrey Lozhkin, Nageswara R. Madamanchi, Katherine F. Campbell, Todd J. Herron
Summary: A model of ischemic heart disease was successfully created using human induced pluripotent stem cell-derived cardiomyocytes, exhibiting many characteristics similar to ischemic cardiomyocytes. This provides a new opportunity for the study of human ischemic heart disease.
Article
Multidisciplinary Sciences
Rodrigo Aguayo-Ortiz, Jeffery Creech, Eric N. Jimenez-Vazquez, Guadalupe Guerrero-Serna, Nulang Wang, Andre Monteiro da Rocha, Todd J. Herron, L. Michel Espinoza-Fonseca
Summary: Membrane proteins are a significant part of the human proteome, offering potential therapeutic targets. Utilizing a combination of computational simulations and experimental methods, this study successfully activated the cardiac Ca2+ pump (SERCA2a) in human iPSC-derived cardiac cells, demonstrating the safety of directly targeting SERCA2a activation as a therapeutic approach. This novel multiscale platform streamlines the identification of drug-like candidates, accelerating the design of effective therapies targeting membrane protein domains.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Eric N. Jimenez-Vazquez, Michael Arad, Alvaro Macias, Maria L. Vera-Pedrosa, Francisco Miguel Cruz, Lilian K. Gutierrez, Ashley J. Cuttita, Andre Monteiro da Rocha, Todd J. Herron, Daniela Ponce-Balbuena, Guadalupe Guerrero-Serna, Ofer Binah, Daniel E. Michele, Jose Jalife
Summary: This study found dysfunction of the Na(V)1.5-Kir2.1 channelosome in iPSC-CMs derived from patients with Duchenne Muscular Dystrophy (DMD) cardiomyopathy, resulting in decreased cardiac excitability and conduction. This dysfunction can be rescued by the scaffolding protein alpha 1-syntrophin to restore excitability and prevent arrhythmias.
Article
Multidisciplinary Sciences
Andrew Allan, Jeffery Creech, Christian Hausner, Peyton Krajcarski, Bianca Gunawan, Noah Poulin, Paul Kozlowski, Christopher Wayne Clark, Rachel Dow, Prakaimuk Saraithong, Devin B. Mair, Travis Block, Andre Monteiro da Rocha, Deok-Ho Kim, Todd J. Herron
Summary: To improve the maturity of hiPSC-CMs, researchers developed a perinatal stem cell-derived extracellular matrix coating and a cardiac optical mapping device. These tools provided new biological insights into mature hiPSC-CMs, including their chamber-specific characteristics, response to cardioactive drugs, and changes in calcium signaling.
Meeting Abstract
Obstetrics & Gynecology
Michael Balistreri, Justin A. Davis, Andre Monteiro da Rocha, Katherine F. Campbell, Marjorie C. Treadwell, Todd J. Herron
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2017)
Meeting Abstract
Cardiac & Cardiovascular Systems
Andre Monteiro da Rocha, Guadalupe Guerrero-Serna, Adam Helms, Carly Luzod, Sergey Mironov, Mark Russell, Jose Jalife, Sharlene M. Day, Gary D. Smith, Todd J. Herron
Meeting Abstract
Cardiac & Cardiovascular Systems
Katherine Campbell, Justin Davis, Andre Monteiro da Rocha, Guadalupe Guerrero-Serna, Xiang Li, Lakshmi Mundada, Evan Hoopingarner, Adam Helms, Sharlene Day, Jose Jalife, Jianping Fu, Todd J. Herron