Human cells behaving like those at a crucial embryological milestone have been identified, enabling insights into early development.
Early human embryo research is permitted in the UK, but strict regulations preventing research on embryos older than 14 days means that non-human models are needed. Researchers at the Babraham Institute, Cambridge have identified human embryonic stem cells (ESCs) whose biology resembles that of human embryo cells at the eight-cell (8C) stage.
Dr Jasmin Taubenschmid-Stowers of the Babraham Institute and lead author of the study said: 'Studying mouse embryonic stem cells has allowed researchers to learn about the general process of genome activation, but we could learn even more about this important step in human development thanks to our discovery of a human stem cell counterpart.'
The report, published in Cell Stem Cell, shows how the team sequenced the RNA of single cells within a population of cultured human ESCs to identify subsets whose gene expression reflected that of 8C embryo cells. They named them eight-cell like cells (8CLCs).
At this stage of embryogenesis, cells undergo a process called zygote genome activation when the cells' DNA is restructured, triggering the actviation of genes required for different parts of the embryo to being forming.
The team found that not only did the cells resemble 8C cells at the level of their gene expression, but proteins involved in this transition accumulated in much the same way as their in vivo counterparts. The work also revealed a potential novel role for two genes in human embryogenesis.
In their paper the authors suggested: 'The appearance, maintenance, and enrichment of 8CLCs will allow the study of genome activation in culture and make it amenable to genetic and pharmacological manipulation in a high-throughput way,'
The researchers hope this discovery will open the door to a detailed understanding of the zygotic genome activation in a system which is more relevant to human biology than current non-human models.
'Our focus is now to characterise these cells and understand their unique properties so that we can use 8-cell like cells as a tool to ask questions about the molecular changes that may cause developmental issues at this early stage', explained Professor Wolf Reik of the Babraham Institute and corresponding author of the study.
Sources and References
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New stem cell population provides a new way to study the awakening of the human genome
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8C-like cells capture the human zygotic genome activation program in vitro
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Human embryo at 8-cell stage modeled in new stem cell culture
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Researchers discover new stem cell population that closely matches existing human stem cells
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