Heart Enhancers with Deeply Conserved Regulatory Activity Are Established Early in Development
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1 Early Patterning and Specification of Cardiac Progenitors In
Early Patterning and Specification of Cardiac Progenitors in Gastrulating Mesoderm W. Patrick Devine1,2,3,4, Joshua D. Wythe1,2, Matthew George1,2,5 , Kazuko Koshiba- Takeuchi1,2, Benoit G. Bruneau1,2,4,5 1. Gladstone Institute of Cardiovascular Disease, San Francisco, CA, 94158 USA 2. Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA 3. Department of Pathology, University of California, San Francisco, CA 94143 USA 4. Cardiovascular Research Institute, University of California, San Francisco, CA 94158 USA 5. Developmental and Stem Cell Biology Program, University of San Francisco, CA 94143, USA 6. Department of Pediatrics, University of California, San Francisco, CA 94143 USA Competing interests statement: The authors declare no competing interests. 1 Abstract Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor "fields" has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies. -
Co-Occupancy by Multiple Cardiac Transcription Factors Identifies
Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart Aibin Hea,b,1, Sek Won Konga,b,c,1, Qing Maa,b, and William T. Pua,b,2 aDepartment of Cardiology and cChildren’s Hospital Informatics Program, Children’s Hospital Boston, Boston, MA 02115; and bHarvard Stem Cell Institute, Harvard University, Cambridge, MA 02138 Edited by Eric N. Olson, University of Texas Southwestern, Dallas, TX, and approved February 23, 2011 (received for review November 12, 2010) Identification of genomic regions that control tissue-specific gene study of a handful of model genes (e.g., refs. 7–10), it has not been expression is currently problematic. ChIP and high-throughput se- evaluated using unbiased, genome-wide approaches. quencing (ChIP-seq) of enhancer-associated proteins such as p300 In this study, we used a modified ChIP-seq approach to define identifies some but not all enhancers active in a tissue. Here we genome wide the binding sites of these cardiac TFs (1). We show that co-occupancy of a chromatin region by multiple tran- provide unbiased support for collaborative TF interactions in scription factors (TFs) identifies a distinct set of enhancers. GATA- driving cardiac gene expression and use this principle to show that chromatin co-occupancy by multiple TFs identifies enhancers binding protein 4 (GATA4), NK2 transcription factor-related, lo- with cardiac activity in vivo. The majority of these multiple TF- cus 5 (NKX2-5), T-box 5 (TBX5), serum response factor (SRF), and “ binding loci (MTL) enhancers were distinct from p300-bound myocyte-enhancer factor 2A (MEF2A), here referred to as cardiac enhancers in location and functional properties. -
Supraphysiological Levels of Oxygen Exposure During the Neonatal
www.nature.com/scientificreports OPEN Supraphysiological Levels of Oxygen Exposure During the Neonatal Period Impairs Signaling Received: 15 January 2018 Accepted: 4 June 2018 Pathways Required for Learning Published: xx xx xxxx and Memory Manimaran Ramani1, Ranjit Kumar2, Brian Halloran1, Charitharth Vivek Lal1, Namasivayam Ambalavanan 1,3 & Lori L. McMahon3,4 Preterm infants often require prolonged oxygen supplementation and are at high risk of neurodevelopmental impairment. We recently reported that adult mice exposed to neonatal hyperoxia (postnatal day [P] 2 to 14) had spatial navigation memory defcits associated with hippocampal shrinkage. The mechanisms by which early oxidative stress impair neurodevelopment are not known. Our objective was to identify early hyperoxia-induced alterations in hippocampal receptors and signaling pathways necessary for memory formation. We evaluated C57BL/6 mouse pups at P14, exposed to either 85% oxygen or air from P2 to 14. We performed targeted analysis of hippocampal ligand-gated ion channels and proteins necessary for memory formation, and global bioinformatic analysis of diferentially expressed hippocampal genes and proteins. Hyperoxia decreased hippocampal mGLU7, TrkB, AKT, ERK2, mTORC1, RPS6, and EIF4E and increased α3, α5, and ɤ2 subunits of GABAA receptor and PTEN proteins, although changes in gene expression were not always concordant. Bioinformatic analysis indicated dysfunction in mitochondria and global protein synthesis and translational processes. In conclusion, supraphysiological oxygen exposure reduced proteins necessary for hippocampus-dependent memory formation and may adversely impact hippocampal mitochondrial function and global protein synthesis. These early hippocampal changes may account for memory defcits seen in preterm survivors following prolonged oxygen supplementation. Children born preterm with a relatively uncomplicated neonatal intensive care unit course ofen have defcits in executive function and learning and memory1–3. -
Stages of Embryonic Development of the Zebrafish
DEVELOPMENTAL DYNAMICS 2032553’10 (1995) Stages of Embryonic Development of the Zebrafish CHARLES B. KIMMEL, WILLIAM W. BALLARD, SETH R. KIMMEL, BONNIE ULLMANN, AND THOMAS F. SCHILLING Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403-1254 (C.B.K., S.R.K., B.U., T.F.S.); Department of Biology, Dartmouth College, Hanover, NH 03755 (W.W.B.) ABSTRACT We describe a series of stages for Segmentation Period (10-24 h) 274 development of the embryo of the zebrafish, Danio (Brachydanio) rerio. We define seven broad peri- Pharyngula Period (24-48 h) 285 ods of embryogenesis-the zygote, cleavage, blas- Hatching Period (48-72 h) 298 tula, gastrula, segmentation, pharyngula, and hatching periods. These divisions highlight the Early Larval Period 303 changing spectrum of major developmental pro- Acknowledgments 303 cesses that occur during the first 3 days after fer- tilization, and we review some of what is known Glossary 303 about morphogenesis and other significant events that occur during each of the periods. Stages sub- References 309 divide the periods. Stages are named, not num- INTRODUCTION bered as in most other series, providing for flexi- A staging series is a tool that provides accuracy in bility and continued evolution of the staging series developmental studies. This is because different em- as we learn more about development in this spe- bryos, even together within a single clutch, develop at cies. The stages, and their names, are based on slightly different rates. We have seen asynchrony ap- morphological features, generally readily identi- pearing in the development of zebrafish, Danio fied by examination of the live embryo with the (Brachydanio) rerio, embryos fertilized simultaneously dissecting stereomicroscope. -
The Use of Phosphoproteomic Data to Identify Altered Kinases and Signaling Pathways in Cancer
The use of phosphoproteomic data to identify altered kinases and signaling pathways in cancer By Sara Renee Savage Thesis Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE in Biomedical Informatics August 10, 2018 Nashville, Tennessee Approved: Bing Zhang, Ph.D. Carlos Lopez, Ph.D. Qi Liu, Ph.D. ACKNOWLEDGEMENTS The work presented in this thesis would not have been possible without the funding provided by the NLM training grant (T15-LM007450) and the support of the Biomedical Informatics department at Vanderbilt. I am particularly indebted to Rischelle Jenkins, who helped me solve all administrative issues. Furthermore, this work is the result of a collaboration between all members of the Zhang lab and the larger CPTAC consortium. I would like to thank the other CPTAC centers for processing the data, and Chen Huang and Suhas Vasaikar in the Zhang lab for analyzing the colon cancer copy number and proteomic data, respectively. All members of the Zhang lab have been extremely helpful in answering any questions I had and offering suggestions on my work. Finally, I would like to acknowledge my mentor, Bing Zhang. I am extremely grateful for his guidance and for giving me the opportunity to work on these projects. ii TABLE OF CONTENTS Page ACKNOWLEDGEMENTS ................................................................................................ ii LIST OF TABLES............................................................................................................ -
Transcriptomic Insights Into the Vertebrate Phylotypic Stage
RIKEN Center for Developmental Biology (CDB) 2‐2‐3 Minatojima minamimachi, Chuo‐ku, Kobe 650‐0047, Japan Transcriptomic insights into the vertebrate phylotypic stage April 10, 2011 – The concept of the phylotypic stage traces its roots back to early comparative observations of embryos from different vertebrate taxa, in which it was noted that embryonic morphologies appeared to converge on a shared body plan before veering off in specialized directions. This gave rise to a profound debate over the evolutionary basis for this phenomenon; specifically, whether it could best be explained by a “funnel” model, in which the commonality of traits is highest at the earliest stages of embryogenesis, and gradually but unilaterally narrows over time, or an “hourglass” model, where homology is highest at a point later in development as the body plan is being established, and differs more widely before and after. Funnel (left) and hourglass (right) models of changes in commonality and diversity in vertebrate ontogeny. A new comparative transcriptomic analysis of four vertebrate species conducted by Naoki Irie in the Laboratory for Evolutionary Morphology (Shigeru Kuratani, Group Director) has now revealed that genetic expression is most highly conserved across taxa at the pharyngula stage of development. Published in Nature Communications, these latest findings strongly suggest that the hourglass model is the more accurate description of how the vertebrate phylotype manifests. Irie decision to study this question using a gene expression approach broke with the long history of morphological comparisons. He sampled tissue from mouse, chicken, and frog embryos across multiple developmental stages to allow for comparisons of changes in gene expression, and further supplemented this data set with information from previously published transcriptomic studies in a fourth taxa, zebrafish, thus providing representative samples from mammal, bird, amphibian and fish species. -
Constrained Vertebrate Evolution by Pleiotropic Genes
ARTICLES DOI: 10.1038/s41559-017-0318-0 Constrained vertebrate evolution by pleiotropic genes Haiyang Hu 1,2, Masahiro Uesaka3, Song Guo1, Kotaro Shimai4, Tsai-Ming Lu 5, Fang Li6, Satoko Fujimoto7, Masato Ishikawa8, Shiping Liu6, Yohei Sasagawa9, Guojie Zhang6,10, Shigeru Kuratani7, Jr-Kai Yu 5, Takehiro G. Kusakabe 4, Philipp Khaitovich1, Naoki Irie 3,11* and the EXPANDE Consortium Despite morphological diversification of chordates over 550 million years of evolution, their shared basic anatomical pattern (or ‘bodyplan’) remains conserved by unknown mechanisms. The developmental hourglass model attributes this to phylum- wide conserved, constrained organogenesis stages that pattern the bodyplan (the phylotype hypothesis); however, there has been no quantitative testing of this idea with a phylum-wide comparison of species. Here, based on data from early-to-late embryonic transcriptomes collected from eight chordates, we suggest that the phylotype hypothesis would be better applied to vertebrates than chordates. Furthermore, we found that vertebrates’ conserved mid-embryonic developmental programmes are intensively recruited to other developmental processes, and the degree of the recruitment positively correlates with their evolutionary conservation and essentiality for normal development. Thus, we propose that the intensively recruited genetic system during vertebrates’ organogenesis period imposed constraints on its diversification through pleiotropic constraints, which ultimately led to the common anatomical pattern observed in vertebrates. ver the past 550 million years, the basic anatomical features comparisons of species to confirm that the most transcriptomi- (or ‘bodyplan’) of animals at the phylum level have been con- cally conserved mid-embryonic period actually accounts for phy- Oserved1,2. However, potential mechanisms underlying this lotype or bodyplan-defining stages. -
Supplementary Figure 1. Network Map Associated with Upregulated Canonical Pathways Shows Interferon Alpha As a Key Regulator
Supplementary Figure 1. Network map associated with upregulated canonical pathways shows interferon alpha as a key regulator. IPA core analysis determined interferon-alpha as an upstream regulator in the significantly upregulated genes from RNAseq data from nasopharyngeal swabs of COVID-19 patients (GSE152075). Network map was generated in IPA, overlaid with the Coronavirus Replication Pathway. Supplementary Figure 2. Network map associated with Cell Cycle, Cellular Assembly and Organization, DNA Replication, Recombination, and Repair shows relationships among significant canonical pathways. Significant pathways were identified from pathway analysis of RNAseq from PBMCs of COVID-19 patients. Coronavirus Pathogenesis Pathway was also overlaid on the network map. The orange and blue colors in indicate predicted activation or predicted inhibition, respectively. Supplementary Figure 3. Significant biological processes affected in brochoalveolar lung fluid of severe COVID-19 patients. Network map was generated by IPA core analysis of differentially expressed genes for severe vs mild COVID-19 patients in bronchoalveolar lung fluid (BALF) from scRNA-seq profile of GSE145926. Orange color represents predicted activation. Red boxes highlight important cytokines involved. Supplementary Figure 4. 10X Genomics Human Immunology Panel filtered differentially expressed genes in each immune subset (NK cells, T cells, B cells, and Macrophages) of severe versus mild COVID-19 patients. Three genes (HLA-DQA2, IFIT1, and MX1) were found significantly and consistently differentially expressed. Gene expression is shown per the disease severity (mild, severe, recovered) is shown on the top row and expression across immune cell subsets are shown on the bottom row. Supplementary Figure 5. Network map shows interactions between differentially expressed genes in severe versus mild COVID-19 patients. -
A Perspective from Embryology
The Proceedings of the International Conference on Creationism Volume 3 Print Reference: Pages 547-560 Article 46 1994 The Genesis Kinds: A Perspective from Embryology Sheena E.B. Tyler Follow this and additional works at: https://digitalcommons.cedarville.edu/icc_proceedings DigitalCommons@Cedarville provides a publication platform for fully open access journals, which means that all articles are available on the Internet to all users immediately upon publication. However, the opinions and sentiments expressed by the authors of articles published in our journals do not necessarily indicate the endorsement or reflect the views of DigitalCommons@Cedarville, the Centennial Library, or Cedarville University and its employees. The authors are solely responsible for the content of their work. Please address questions to [email protected]. Browse the contents of this volume of The Proceedings of the International Conference on Creationism. Recommended Citation Tyler, Sheena E.B. (1994) "The Genesis Kinds: A Perspective from Embryology," The Proceedings of the International Conference on Creationism: Vol. 3 , Article 46. Available at: https://digitalcommons.cedarville.edu/icc_proceedings/vol3/iss1/46 THE GENESIS KINDS: A PERSPECTIVE FROM EMBRYOLOGY SHEENA E.B. TYLER, PhD, BSc. c/o PO Box 22, Rugby, Warwickshire, CV22 7SY, England. ABSTRACT From the days of greatest antiquity. mankind has recognised the distinctive common attributes shared by living things, and has attempted to relate these groups together by devising classification systems - the science of taxonomy or systematics. Much contemporary systematics invokes continuity in order to construct continuous transformational series. By contrast, the taxic or typological paradigm, which can be traced to the pre-Darwinian era, has gained preference over the transformational one in some secular circles [10; reviewed in 42). -
The Body Plan Concept and Its Centrality in Evo-Devo
Evo Edu Outreach (2012) 5:219–230 DOI 10.1007/s12052-012-0424-z EVO-DEVO The Body Plan Concept and Its Centrality in Evo-Devo Katherine E. Willmore Published online: 14 June 2012 # Springer Science+Business Media, LLC 2012 Abstract A body plan is a suite of characters shared by a by Joseph Henry Woodger in 1945, and means ground plan group of phylogenetically related animals at some point or structural plan (Hall 1999; Rieppel 2006; Woodger 1945). during their development. The concept of bauplane, or body Essentially, a body plan is a suite of characters shared by a plans, has played and continues to play a central role in the group of phylogenetically related animals at some point study of evolutionary developmental biology (evo-devo). during their development. However, long before the term Despite the importance of the body plan concept in evo- body plan was coined, its importance was demonstrated in devo, many researchers may not be familiar with the pro- research programs that presaged the field of evo-devo, per- gression of ideas that have led to our current understanding haps most famously (though erroneously) by Ernst Haeck- of body plans, and/or current research on the origin and el’s recapitulation theory. Since the rise of evo-devo as an maintenance of body plans. This lack of familiarity, as well independent field of study, the body plan concept has as former ties between the body plan concept and metaphys- formed the backbone upon which much of the current re- ical ideology is likely responsible for our underappreciation search is anchored. -
Downregulation of Carnitine Acyl-Carnitine Translocase by Mirnas
Page 1 of 288 Diabetes 1 Downregulation of Carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretion Mufaddal S. Soni1, Mary E. Rabaglia1, Sushant Bhatnagar1, Jin Shang2, Olga Ilkayeva3, Randall Mynatt4, Yun-Ping Zhou2, Eric E. Schadt6, Nancy A.Thornberry2, Deborah M. Muoio5, Mark P. Keller1 and Alan D. Attie1 From the 1Department of Biochemistry, University of Wisconsin, Madison, Wisconsin; 2Department of Metabolic Disorders-Diabetes, Merck Research Laboratories, Rahway, New Jersey; 3Sarah W. Stedman Nutrition and Metabolism Center, Duke Institute of Molecular Physiology, 5Departments of Medicine and Pharmacology and Cancer Biology, Durham, North Carolina. 4Pennington Biomedical Research Center, Louisiana State University system, Baton Rouge, Louisiana; 6Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, New York. Corresponding author Alan D. Attie, 543A Biochemistry Addition, 433 Babcock Drive, Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, (608) 262-1372 (Ph), (608) 263-9608 (fax), [email protected]. Running Title: Fatty acyl-carnitines enhance insulin secretion Abstract word count: 163 Main text Word count: 3960 Number of tables: 0 Number of figures: 5 Diabetes Publish Ahead of Print, published online June 26, 2014 Diabetes Page 2 of 288 2 ABSTRACT We previously demonstrated that micro-RNAs 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of micro-RNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including non-fuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT, Slc25a20) is a direct target of these miRNAs. -
Genome-Wide Screening Identifies Genes and Biological Processes
Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 10-12-2018 Genome-Wide Screening Identifies Genes and Biological Processes Implicated in Chemoresistance and Oncogene-Induced Apoptosis Tengyu Ko Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Cancer Biology Commons, Cell Biology Commons, and the Genomics Commons Recommended Citation Ko, Tengyu, "Genome-Wide Screening Identifies Genes and Biological Processes Implicated in Chemoresistance and Oncogene- Induced Apoptosis" (2018). LSU Doctoral Dissertations. 4715. https://digitalcommons.lsu.edu/gradschool_dissertations/4715 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. GENOME-WIDE SCREENING IDENTIFIES GENES AND BIOLOGICAL PROCESSES IMPLICATED IN CHEMORESISTANCE AND ONCOGENE- INDUCED APOPTOSIS A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical and Veterinary Medical Sciences through the Department of Comparative Biomedical Sciences by Tengyu Ko B.S., University of California, Santa Barbara 2010 December 2018 ACKNOWLEDGEMENTS I would like to express my sincerest gratitude to my major supervisor Dr. Shisheng Li for giving me the opportunity to join his team and the freedom to pursue projects. I appreciate all of his thoughts and efforts. Truly, none of these findings would be possible without his supervisions, supports, insightful discussions, and patience.