Examining the State of the Science of Mammalian Embryo Model Systems: Proceedings of a Workshop (2020)
Chapter: Front Matter
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
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
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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: 978-0-309-67668-7
International Standard Book Number-10: 0-309-67668-1
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.
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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.
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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 & 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
___________________
1 The 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.
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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.
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Contents
Opportunities and Challenges with Stem Cell–Based Embryo Models
New Models May Offer a New Frontier of Data
Organization of the Proceedings of a Workshop
2 MAMMALIAN EMBRYO RESEARCH AND PLURIPOTENT STEM CELLS
Molecular Mechanisms of Lineage Specification in Human Embryos
Building Embryo Models to Study Human Development
Clinical Perspective on Pre-Implantation Human Embryo Development
3 EXAMINING THE DEVELOPMENT OF EXTRAEMBRYONIC LINEAGES
Modeling Trophoblast Differentiation Using Pluripotent Stem Cells
Nature of Trophoblast Generated from Embryonic and Induced Pluripotent Stem Cells
Molecular Innovation in the Human Trophoblast Lineage
4 STEM CELL–BASED MODELS OF HUMAN EMBRYOS
Gastruloids: Modeling Human Embryos and Embryonic Tissues
Modeling Human Development in 2D with Micropatterns
Blastoids: Modeling the Pre-Implantation Embryo
Microfluidic Stem Cell Model of Peri-Implantation
5 COMPARATIVE EMBRYONIC DEVELOPMENT ACROSS SPECIES
Cross-Species Comparison of Pre-Implantation Chromosomal Instability
Trophoblast Differentiation from Primate Pluripotent Cells
Early Neural Crest Formation: From Birds to Humans
Blastocyst-Like Structures Generated from Pluripotent Stem Cells with Expanded Potential
6 EXPLORING OPPORTUNITIES AND CHALLENGES WITH MAMMALIAN EMBRYO MODEL SYSTEMS
Human Pluripotent Stem Cells, the Human Embryo, and the Self-Renewing State
Using Embryo Models to Understand Human Development
Boxes and Figures
BOXES
2-1 Regulatory Framework for Human Embryonic Research in the United Kingdom
3-1 Pluripotent Versus Totipotent Stem Cells
3-2 Data Collected on the BAP-Treated hESC Model of Trophoblast Differentiation
4-1 Rationale for Human Embryological Studies
4-2 Key Features of the Blastoid
FIGURES
3-1 Human trophoblast differentiation
3-2 The hourglass model of variation in early development
4-1 TGFβ signals and cell fates in human embryonic stem cells
4-2 Mouse blastocyst at day 4.5 (100 cells)
5-1 Blastocyst-like structure generated in vitro using expanded- or extended-potential stem cells
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Acronyms and Abbreviations
| BLIMP1 | B-lymphocyte-induced maturation protein 1 |
| BMP4 | bone morphogenetic protein 4 |
| BRA | BRACHYURY |
| CAG | cytosine-adenine-guanine |
| CDX2 | caudal type homeobox 2 |
| CG | chorionic gonadotropin |
| CGA | alpha peptide of chorionic gonadotropin |
| CGB | beta peptide of chorionic gonadotropin |
| CTB | cytotrophoblast |
| DHEA-S | dehydroepiandrosterone sulfate |
| 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 |
| 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 |
| KLF4 | Krüppel-like factor 4 |
| MEK/ERK | mitogen-activated protein kinase/extracellular-signal-regulated kinase |
| MMP | matrix metalloproteinase |
| 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 |
| PSC | pluripotent stem cell |
| REC | Research Ethics Committee |
| SNAIL | Zinc finger protein SNAI1 |
| SNP | single-nucleotide polymorphism |
| SOX | SRY-related HMG-box family of 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 | extraembryonic endoderm |
| YAP1 | yes-associated protein 1 |
| ysTE | yolk sac trophectoderm |
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