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Scientists open the black box of the milestone stage of human embryonic development for the first time

For the first time, scientists based at Helmholtz Munich and the University of Oxford were able to shed light on one of the most critical stages of human embryonic development (gastrulation). The finding, published in the journal Nature, will catalyze the improvement of experimental stem cell models and will drive future studies to unravel the secrets of human development.

Human Embryo at the Gastrulation stage. © Shankar Srivinas

Gastrulation is one of the most critical stages of early embryonic development, which takes place between days 14 and 21 after fertilization. During this step, there is an explosion of cell diversification and the different cells get ready to form the specific organs and body tissues later in development. Until now, there is very little understanding of human gastrulation, because samples at these stages are exceptionally rare and researchers can only legally culture human embryos up to the equivalent of 14 days after fertilization. Thus, our current knowledge is mostly based on findings from model systems, such as mouse or chicken, or cell culture-based models for human embryos.

„Not being able to compare such in vitro models against what actually happens in vivo means that we are not yet able to understand how closely these models recapitulate the gastrulation process in humans”, explains Antonio Scialdone, co-corresponding author of this study.

Opening up the black box of human development
The team of researchers analyzed a human embryo at the gastrulation stage that was generously donated to research by a donor after termination of her pregnancy, through the Human Developmental Biology resource in the UK (https://www.hdbr.org) and according to the strictest ethical standards as described therein. To gain the most information from such a precious sample, the researchers used single-cell RNA-sequencing to measure the gene expression levels in cells from three regions of the embryo. In doing so, they were able to identify 11 cell populations and the changes associated with their differentiation paths.
 
“For example, we identified a population of cells corresponding to blood progenitors, which go on to form the different blood components. Interestingly, in a comparison with mouse embryos, we found evidence that blood formation in humans might be further progressed than in mouse embryos at equivalent stages. But overall our study provides valuable insights that at the molecular level, mouse can serve as a model for human development“, says Elmir Mahammadov first co-author of the paper.

The study paves the way for unraveling the secrets of human development  
This study is a milestone for developmental biology as human samples at these early stages are exceptionally rare. Thus, the team of researchers made the raw data available to the research community on an open-access website prior to publication, allowing an interactive exploration of these data (http://www.human-gastrula.net). “We have now the opportunity to further our current understanding of human development. Our findings will help interpret experimental results on gastrulation from model organisms or in vitro models and the data provide  a valuable resource for refining approaches for the directed differentiation of human stem cells in vitro“, says Shankar Srinivas, who led the study from the Oxford side.

About the people

Elmir Mahammadov and Antonio Scialdone are part of the Institute for Epigenetics and Stem Cells, Institute of Functional Epigenetics, and Institute of Computational Biology at Helmholtz Munich. At the University of Oxford, Shankar Srinivas, from the Department of Physiology, Anatomy and Genetics, led the study from the UK side.

Original publication
Tyser et al., 2021: Single-cell transcriptomic characterization of a gastrulating human embryo. Nature, DOI: 10.1016/S2542-5196(21)00195-9.