Proteins that exist in the junctions between cells have been shown to help create signalling gradients crucial for cell differentiation in human embryo models.
As cells divide and grow in a developing embryo, they differentiate to take on specific roles or identities. This must happen in the right places at the right times for the body to form appropriately. Researchers at the Gladstone Institutes, San Francisco, California have uncovered how proteins called tight junctions help to coordinate this by controlling molecular signals.
'This study has exciting implications for the way we design gastrulation models and other lab techniques for differentiating stem cells into specialised cell types,' said Professor Shinya Yamanaka of the Gladstone Institutes, Nobel Prize winner and corresponding author of the study published in Developmental Cell. He continued: 'The better we understand signaling mechanisms in embryos, the more easily we can recapitulate these processes in robust, reproducible ways.'
The study describes how scientists wanted to figure out why adding a single molecular signal called BMP4 to in vitro human pluripotent stem cells could stimulate the formation of different cell types, that go on to form the three tissue layers formed during gastrulation: ectoderm, mesoderm and endoderm.
'This has been kind of a head scratcher in the field,' said Dr Ivana Vasic of the Gladstone institutes and lead author of the study. She said: 'all these cells are either interpreting the same cue from BMP4 differently, or they're not really getting the same cue.'
Researchers found gradients of signalling molecules, such as BMP4, are fundamental in the initiation of the formation of the three tissue layers during gastrulation. Tight junctions were found to be responsible for the formation of these gradients, that differentiated response to BMP4, they discovered.
'We showed that removing the tight junctions made all the cells respond to BMP4,' said Professor Yamanaka. 'This suggests that tight junctions block cells from responding to signals in gastrulation models, and more fundamentally, that the structure of cells is very important to how they receive differentiation signals.'
Embryo models are crucial to the research of human development, given the scarce availability of early human embryos and legal restrictions such as the UK's 14-day rule. The findings of this study could help progress the development of embryo models for research.
During the work, the authors discovered that by disrupting tight junctions, they could generate cells that resemble precursors to human sperm and egg cells, which could have implications for fertility treatments in the future.
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