Human embryogenesis

Abstract: Carnegie Stages of Early Human Embryonic Development (Weeks 1-8) Major Developmental Events During the Fetal Period Part I: Early Development and the Fetal-Maternal Relationship Chapter 1: Getting Ready for Pregnancy Gametogenesis Preparation of the Female Reproductive Tract For Pregnancy Hormonal Interactions Involved with Reproduction in Males Chapter 2: Transport of Gametes and Fertilization Ovulation and Egg and Sperm Transport Fertilization Chapter 3: Cleavage and Implantation Cleavage Embryo Transport and Implantation Chapter 4: Molecular Basis for Embryonic Development Fundamental Molecular Processes in Development Chapter 5: Formation of Germ Layers and Early Derivatives Two-Germ-Layer Stage Gastrulation and the Three Embryonic Germ Layers Induction of the Nervous System Cell Adhesion Molecules Chapter 6: Establishment of the Basic Embryonic Body Plan Development of the Ectodermal Germ Layer Development of the Mesodermal Germ Layer Development of the Endodermal Germ Layer Basic Structure of the 4-Week Old Embryo Chapter 7: Placenta and Extraembryonic Membranes Extraembryonic Tissues Chorion and Placenta Placenta After Birth Placenta and Membranes in Multiple Pregnancies Chapter 8: Developmental Disorders: Causes, Mechanisms, and Patterns General Principles Causes of Malformations Developmental Disturbances Resulting in Malformations Part II: Development of the Body Systems Chapter 9: Integumentary, Skeletal and Muscular Systems Integumentary System Skeleton Muscular System Chapter 10: Limb Development Initiation of Limb Development Regulative Properties and Axial Determination Outgrowth of the Limb Bud Morphogenetic Control of Early Limb Development Development of Limb Tissues Chapter 11: Nervous System Establishment of the Nervous System Early Shaping of the Nervous System Histogenesis Within the Central Nervous System Craniocaudal Pattern Formation and Segmentation Peripheral Nervous System Autonomic Nervous System Later Structural Changes in the Central Nervous System Ventricles, Meninges, and Cerebrospinal Fluid Formation Cranial Nerves Development of Neural Function Chapter 12: Neural Crest Origins of the Neural Crest Migrations of the Neural Crest Differentiation of Neural Crest Cells Major Divisions of the Neural Crest Trunk Neural Crest Circumpharyngeal Neural Crest Cranial Neural Crest Chapter 13: Sense Organs Eye Ear Chapter 14: Head and Neck Early Development of the Head and Neck Fundamental Organization of the Pharyngeal Region Development of the Facial Region Development of the Pharynx and Its Derivatives Chapter 15: Digestive and Respiratory Systems and Body Cavities Digestive System Respiratory System Body Cavities Chapter 16: Urogenital System Urinary System Genital System Sexual Duct System External Genitalia Chapter 17: Cardiovascular System Developmental of the Vascular System Developmental and Partitioning of the Heart Initiation of Cardiac Function Fetal Circulation Chapter 18: Fetal Period and Birth Growth and Form of the Fetus Fetal Physiology Parturition Adaptations to Postnatal Life Overview Answers to Clinical Vignettes and Review Questions

Abstract: Here, we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast, including the transcription factor KLF17. Key components of the TGF-β signalling pathway, including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1, are also enriched in the human epiblast. Intriguingly, inhibition of TGF-β signalling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although the key trophectoderm factors Id2, Elf5 and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics, including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparison of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared with mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells.

Abstract: Early human embryonic development involves extensive lineage diversification, cell-fate specification and tissue patterning1. Despite its basic and clinical importance, early human embryonic development remains relatively unexplained owing to interspecies divergence2,3 and limited accessibility to human embryo samples. Here we report that human pluripotent stem cells (hPSCs) in a microfluidic device recapitulate, in a highly controllable and scalable fashion, landmarks of the development of the epiblast and amniotic ectoderm parts of the conceptus, including lumenogenesis of the epiblast and the resultant pro-amniotic cavity, formation of a bipolar embryonic sac, and specification of primordial germ cells and primitive streak cells. We further show that amniotic ectoderm-like cells function as a signalling centre to trigger the onset of gastrulation-like events in hPSCs. Given its controllability and scalability, the microfluidic model provides a powerful experimental system to advance knowledge of human embryology and reproduction. This model could assist in the rational design of differentiation protocols of hPSCs for disease modelling and cell therapy, and in high-throughput drug and toxicity screens to prevent pregnancy failure and birth defects.