A new dataset, combining information on cell position and gene expression from an early human embryo, has been made available as a reference for scientists investigating human development.
The study, published in Cell and led by Professor Leqian Yu from the Institute of Stem Cell and Regenerative Medicine in Beijing, China, serves as a reference for researchers working on stem-cell-based embryo models and other mammalian species to compare their results to the actual human embryo. Making the dataset available through an interactive website, the study's authors aim to provide an atlas of human development for others to explore.
The authors explained: 'Gaining insights into the post-implantation development of humans has been challenging. Recently, several stem-cell-derived human embryo models tried to provide an alternative resource to study human early development. However, how to build and evaluate these embryo models is highly difficult due to the lack of natural embryo references.'
Gastrulation is the stage of development when the layers that make all cell types of an organism start to appear in the embryo. Scientists estimate that the process occurs one week after the embryo has implanted in the lining of the womb, and two weeks after fertilisation. Gastrulation involves extensive cell movement and differentiation leading to axis formation, around which the body structure develops.
Current legislation in the UK does not permit human embryos to be cultured in vitro for more than 14 days of development, precluding the study of gastrulation (see BioNews 885, 1152 and 1213). Studying a human embryo undergoing gastrulation is therefore only possible through donation following a termination of pregnancy. Up until now, there was only one other comprehensive dataset characterising a gastrulating human embryo, in which scientists analysed the gene expression of 1195 single cells from a single donated embryo staged at 16-19 days post-fertilisation (see BioNews 1122).
Professor Shankar Srinivas of the University of Oxford, corresponding author of the study from 2021 that constitutes the other dataset, told BioNews: 'The new report from Zhenyu Xiao and colleagues provides integrated information about both the types of cells and their position within a human embryo, so that we can use it to study how these two facets might be interrelated. It provides a valuable resource that can be leveraged by researchers to understand how congenital abnormalities develop, or to generate new cell-based therapies.'
The main addition in the new dataset is the incorporation of positional information. Instead of separating the embryo into individual cells before sequencing, researchers sectioned the intact embryo into 62 slices and sequenced 38,562 spots. Connecting the gene information with the cell location, researchers reconstructed a 3D model of the gastrulating human embryo.
'The authors were able to obtain a post-implantation human embryo at a critical stage where it is clearly undergoing the process of gastrulation,' Professor Robin Lovell-Badge, group leader at the Francis Crick Institute in London and chair of trustees at PET (the Progress Educational Trust – the charity that publishes BioNews) told BioNews. 'This paper is likely to be a very valuable resource for those using stem cell-based embryo models. It is very data-rich and I expect it will be mined for more insight into human embryogenesis.'
He also added: 'The main caveat, however, is that this is data from just a single human embryo – and while it would appear to be normal, this can't be guaranteed. It is also difficult to know the precise stage of the embryo that was obtained. There is clearly a need to obtain a series of embryos undergoing gastrulation and to use these to develop a new detailed staging system based on gene activity and morphology.'
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