National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R1
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R2
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R3
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R4
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R5
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R6
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R7
Page viii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R8
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R9
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R10
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R11
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R12
Page xiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R13
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2020. Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/25779.
×
Page R14

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Examining the State of the Science of Mammalian Embryo Model Systems PROCEEDINGS OF A WORKSHOP Siobhan Addie, Meredith Hackmann, Anna Nicholson, and Sarah H. Beachy, Rapporteurs Board on Health Sciences Policy Health and Medicine Division PREPUBLICATION COPY—Uncorrected Proofs

THE NATIONAL ACADEMIES PRESS   500 Fifth Street, NW   Washington, DC 20001 This activity was supported by a contract between the National Academy of Sciences and the National Institutes of Health (Contract No. HHSN263201800029I; Order No. 75N98019F00854, P00001). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project. International Standard Book Number-13: 978-0-309-XXXXX-X International Standard Book Number-10: 0-309-XXXXX-X Digital Object Identifier: https://doi.org/10.17226/25779 Additional copies of this publication are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu. Copyright 2020 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2020. Examining the state of the science of mammalian embryo model systems: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/25779. PREPUBLICATION COPY—Uncorrected Proofs

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine. Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org. PREPUBLICATION COPY—Uncorrected Proofs

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process, and it represents the position of the National Academies on the statement of task. Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies. For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo. PREPUBLICATION COPY—Uncorrected Proofs

PLANNING COMMITTEE FOR A WORKSHOP ON EXAMINING THE STATE OF THE SCIENCE OF MAMMALIAN EMBRYO MODEL SYSTEMS1 MARTIN PERA (Co-Chair), Professor, The Jackson Laboratory JANET ROSSANT (Co-Chair), Senior Scientist, Developmental and Stem Cell Biology, The Hospital for Sick Children RICHARD BEHRINGER, Professor, Department of Genetics, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center AMANDER CLARK, Professor and Chair, Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles ARNOLD KRIEGSTEIN, John Bowes Distinguished Professor in Stem Cell and Tissue Biology and Founding Director, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco MANA PARAST, Professor in Residence, Pathology, University of California, San Diego RENEE REIJO PERA, Vice President of Research and Economic Development, California Polytechnic State University Board on Health Sciences Policy Staff SARAH H. BEACHY, Senior Program Officer SIOBHAN ADDIE, Program Officer MEREDITH HACKMANN, Associate Program Officer MICHAEL BERRIOS, Research Associate KELLY CHOI, Senior Program Assistant BRIDGET BOREL, Program Coordinator ANDREW M. POPE, Senior Board Director 1The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published proceedings of a workshop rests with the workshop rapporteurs and the institution. v PREPUBLICATION COPY—Uncorrected Proofs

PREPUBLICATION COPY—Uncorrected Proofs

Reviewers This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We thank the following individuals for their review of this proceedings: ANA M. FERARAS, The National Academies of Sciences, Engineering, and Medicine JACK MOSHER, International Society for Stem Cell Research LILIANNA SOLNICA-KREZEL, Washington University in St. Louis Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by LESLIE BENET, University of California, San Francisco. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies. vii PREPUBLICATION COPY—Uncorrected Proofs

PREPUBLICATION COPY—Uncorrected Proofs

Contents ACRONYMS AND ABBREVIATIONS xiii 1 INTRODUCTION AND OVERVIEW 1 Overview of the Workshop, 2 Opportunities and Challenges with Stem Cell–Based Embryo Models, 3 New Models May Offer a New Frontier of Data, 8 Organization of the Proceedings of a Workshop, 8 2 MAMMALIAN EMBRYO RESEARCH AND PLURIPOTENT STEM CELLS 11 Molecular Mechanisms of Lineage Specification in Human Embryos, 12 Building Embryo Models to Study Human Development, 18 Clinical Perspective on Pre-Implantation Human Embryo Development, 22 Panel Discussion, 24 3 EXAMINING THE DEVELOPMENT OF EXTRAEMBRYONIC LINEAGES 29 Modeling Trophoblast Differentiation Using Pluripotent Stem Cells, 30 Nature of Trophoblast Generated from Embryonic and Induced Pluripotent Stem Cells, 36 ix PREPUBLICATION COPY—Uncorrected Proofs

x CONTENTS Molecular Innovation in the Human Trophoblast Lineage, 39 Panel Discussion, 44 4 STEM CELL–BASED MODELS OF HUMAN EMBRYOS 49 Gastruloids: Modeling Human Embryos and Embryonic Tissues, 51 Modeling Human Development in 2D with Micropatterns, 56 Blastoids: Modeling the Pre-Implantation Embryo, 61 Microfluidic Stem Cell Model of Peri-Implantation, 66 Panel Discussion, 70 5 COMPARATIVE EMBRYONIC DEVELOPMENT ACROSS SPECIES 75 Cross-Species Comparison of Pre-Implantation Chromosomal Instability, 76 Trophoblast Differentiation from Primate Pluripotent Cells, 81 Early Neural Crest Formation: From Birds to Humans, 85 Blastocyst-Like Structures Generated from Pluripotent Stem Cells with Expanded Potential, 90 Panel Discussion, 95 6 EXPLORING OPPORTUNITIES AND CHALLENGES WITH MAMMALIAN EMBRYO MODEL SYSTEMS 99 Human Pluripotent Stem Cells, the Human Embryo, and the Self-Renewing State, 99 Final Panel Discussion, 101 Using Embryo Models to Understand Human Development, 104 REFERENCES 107 APPENDIXES A WORKSHOP AGENDA 119 B SPEAKER BIOGRAPHICAL SKETCHES 125 C STATEMENT OF TASK 133 D REGISTERED ATTENDEES 135 PREPUBLICATION COPY—Uncorrected Proofs

Boxes and Figures BOXES 2-1 Regulatory Framework for Human Embryonic Research in the United Kingdom, 13 3-1 Pluripotent Versus Totipotent Stem Cells, 31 3-2 Data Collected on the BAP-Treated hESC Model of Trophoblast Differentiation, 37 4-1 Rationale for Human Embryological Studies, 51 4-2 Key Features of the Blastoid, 64 FIGURES 3-1 Human trophoblast differentiation, 32 3-2 The hourglass model of variation in early development, 40 4-1 TGFβ signals and cell fates in human embryonic stem cells, 57 4-2 Mouse blastocyst at day 4.5 (100 cells), 62 5-1 Blastocyst-like structure generated in vitro using expanded- or extended-potential stem cells, 92 xi PREPUBLICATION COPY—Uncorrected Proofs

PREPUBLICATION COPY—Uncorrected Proofs

Acronyms and Abbreviations BLIMP1 b-lymphocyte-induced maturation protein 1 BMP4 bone morphogenetic protein 4 BRA brachyury CDX2 caudal type homeobox 2 CG chorionic gonadotropin CTB cytotrophoblast EB embryoid body EGF epidermal growth factor EpiSC epiblast-derived stem cell EPSC extended- or expanded-potential pluripotent stem cell ESC embryonic stem cell EVT extravillous trophoblast FGF fibroblast growth factor GATA3 GATA binding protein 3 GCM1 glial cells missing transcription factor 1 GDF growth differentiation factor hCG human chorionic gonadotropin hESC human embryonic stem cell HFEA Human Fertilization and Embryology Authority xiii PREPUBLICATION COPY—Uncorrected Proofs

xiv ACRONYMS AND ABBREVIATIONS HLA-G human leukocyte antigen-G hPSC human pluripotent stem cell ICM inner cell mass IGF1 insulin growth factor iPSC induced pluripotent stem cell IVF in vitro fertilization IWP2 inhibitor of Wnt production-2 MEK/ERK mitogen-activated protein kinase/extracellular-signal- regulated kinase MMP matrix metalloproteinase NANOG Nanog homeobox nEND naïve extraembryonic endoderm (cells) NIH National Institutes of Health Nodal Nodal Growth Differentiation Factor OCT4 octamer-binding transcription factor 4 PE primitive endoderm PGT-A pre-implantation genetic testing for aneuploidy PI3K phosphoinositide 3-kinase POU5F1 POU class 5 homeobox 1 (which encodes OCT4) PSC pluripotent stem cell REC Research Ethics Committee SNAIL Zinc finger protein SNAI1 SNP single-nucleotide polymorphism SOX SRY-related HMG-box genes STB syncytiotrophoblast TDGF1 teratocarcinoma-derived growth factor 1 TE trophectoderm TGFβ transforming growth factor beta TSC trophoblast stem cell VGLL1 vestigial like family member 1 XEN primitive endoderm YAP1 yes-associated protein 1 ysTE yolk sac trophectoderm PREPUBLICATION COPY—Uncorrected Proofs

Next: 1 Introduction and Overview »
Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop Get This Book
×
Buy Paperback | $50.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Because of the recent advances in embryo modeling techniques, and at the request of the Office of Science Policy in the Office of the Director at the National Institutes of Health, the National Academies of Sciences, Engineering, hosted a 1-day public workshop that would explore the state of the science of mammalian embryo model systems. The workshop, which took place on January 17, 2020, featured a combination of presentations, panels, and general discussions, during which panelists and participants offered a broad range of perspectives. Participants considered whether embryo model systems - especially those that use nonhuman primate cells - can be used to predict the function of systems made with human cells. Presentations provided an overview of the current state of the science of in vitro development of human trophoblast. This publication summarizes the presentation and discussion of the workshop.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  6. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  7. ×

    View our suggested citation for this chapter.

    « Back Next »
  8. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!