Modelling post-implantation human development to yolk sac blood emergence
Year: 2023
Type: article
Abstract: Implantation of the human embryo commences a critical developmental stage that comprises profound morphogenetic alteration of embryonic and extra-embryonic tissues, axis formation, and gastrulation events. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons. Additionally, human stem cell models of early post-implantation development with both embryonic and extra-embryonic tissue morphogenesis are lacking. Here, we present iDiscoid, produced from human induced pluripotent stem cells via an engineered a synthetic gene circuit. iDiscoids exhibit reciprocal co-development of human embryonic tissue and engineered extra-embryonic niche in a model of human post-implantation. They exhibit unanticipated self-organization and tissue boundary formation that recapitulates yolk sac-like tissue specification with extra-embryonic mesoderm and hematopoietic characteristics, the formation of bilaminar disc-like embryonic morphology, the development of an amniotic-like cavity, and acquisition of an anterior-like hypoblast pole and posterior-like axis. iDiscoids offer an easy-to-use, high-throughput, reproducible, and scalable platform to probe multifaceted aspects of human early post-implantation development. Thus, they have the potential to provide a tractable human model for drug testing, developmental toxicology, and disease modeling.
Source: Nature
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
Funders: National Science Foundation, University of Pittsburgh, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: G163847046, Request for a Nikon A1 confocal microscope, G3282285992, A Genetically Engineered Human Fetal Liver Niche as a Novel Platform for Biomanufacturing of Hematopoietic Stem Cells, Reconstructing regulatory networks from time series single cell data, Integration of systems and synthetic biology to advance development of human tissues ex vivo, G5726557135, Collaborative Research: RECODE: Directed Differentiation of Human Liver Organoids via Computational Analysis and Engineering of Gene Regulatory Networks, G7657180965, Cellular Approaches to Tissue Engineering and Regeneration, Comprehensive, flexible and FAIR Tools for the HuBMAP HIVE, G9000207989, Pittsburgh Liver Research Center, TriState SenNET (Lung and Heart) Tissue Map and Atlas consortium, Cellular Senescence Network (SenNet) Consortium Organization and Data Coordinating Center (CODCC)
OpenAlex ID: W4389670868