Creating a mouse embryo from stem cells to learn more about the mammalian development process

nature cell biology (2022). DOI: 10.1038/s41556-022-00984-y” width=”800″ height=”530″/>

Proper self-assembly is required for proper morphogenesis. a, Time course of assembly of ETX embryos stained to show E-cadherin (monochrome), Oct4 (red), and Gata4 (green). The bottom row of images are enlargements of the above images and show E-cadherin staining around an evolving cavity as indicated by the dashed yellow lines. The dashed green line indicates the boundary between the ES and XEN compartments. Scale bar, 5 μm. b, Representative images showing Oct4 (red), Gata4 (green), E-cadherin (monochrome), and DAPI (gray) staining in day 4 cadherin OE ETX structures obtained by combining E-cadherin OE ES cells with P-cadherin OE TS cells were formed and wild-type XEN cells. As a control, ETX structures formed by combining wild-type cells were used. Scale bar, 100 μm. c, Comparison and quantification of connected void formation in cadherin OE and control ETX structures. n=361 (control group) and n=253 (cadherin OE group). N = 5 for each condition. Data are presented as means ± standard deviation. Statistical significance was determined by unpaired two-tailed Student’s t-test. d, Representative image with Oct4 (red), Gata4 (green), laminin (monochrome), and DAPI (blue) staining in day 4 cadherin OE ETX structures formed by combining E-cadherin OE ES cells with P-cadherin OE TS cells and wild-type XEN cells. As a control, ETX structures formed by combining wild-type cells were used. Scale bar, 100 μm. e, Quantification of structures containing continuous or discontinuous laminin. n = 40 ETX structures per condition. N=3. Data are presented as means ± standard deviation. Statistical significance was determined by unpaired two-tailed Student’s t-test. f, Principles of self-assembly in stem cell-derived ETX embryos. Differential expression of E-, K-, and P-cadherins allows sorting of ES (epiblast-like), XEN (VE-like), and TS (TE-like) stem cells. Wild-type ES cells with low E-cadherin expression and wild-type TS cells with low P-cadherin expression showed disadvantageous global sorting efficiency. This could be overcome by overexpressing E-cadherin in ES cells and P-cadherin in TS cells to increase the efficiency of ETX embryo formation. Proper morphogenesis, including cavitation, basement membrane formation (purple), and symmetry breaking, can only be observed in well-sorted structures. Numerical data are available as source data. Recognition: nature cell biology (2022). DOI: 10.1038/s41556-022-00984-y

A team of researchers from the California Institute of Technology, in collaboration with a colleague from the Francis Crick Institute and another from the University of Cambridge, both in the UK, have developed a method to grow mouse embryos without using mouse eggs or sperm to produce more learn about early mammalian development. In her article published in the journal nature cell biologythe group describes the use of different types of stem cells to grow mouse embryos.

Previous research has shown that mammalian embryos differentiate into different types of cell masses during their development. Researchers have also found that stem cells are involved in the processes, but the mechanisms responsible are still unknown. In this new experiment, the researchers used three different types of stem cells to grow a mouse embryo that matured to have a beating heart and the beginnings of a brain.

To create such embryos, the researchers first studied the communication between groups of stem cells in naturally developing mouse embryos. They learned to recognize the elements that went into such communications and the means by which they were carried out. Essentially, they “deciphered the code.” They then isolated three main types of stem cells that make up the cell masses in early embryonic development: pluripotent, which eventually grow into body tissue, and two other types, which grow into the amniotic sac and placenta. They also noted the amounts of each type of stem cell.

The next step was to attempt to create a mouse embryo from scratch using the three types of stem cells in a laboratory setting. With careful nurturing, the researchers grew an embryo mature enough to study its development.

To test further, the researchers repeated the procedure but added genetically engineered cells to see how it affected the maturation of the embryo. They found they could replicate some of the same brain development problems seen in human embryos. They suggest their work could also help explain what goes wrong when mice (or humans) miscarry.

Stem cell biologists create new human cell types for research

More information:
Min Bao et al, Synthetic embryos derived from stem cells self-assemble by exploiting cadherin codes and cortical tension, nature cell biology (2022). DOI: 10.1038/s41556-022-00984-y

Citation: Creating a mouse embryo from stem cells to learn more about the mammalian development process (2022 October 7), retrieved October 7, 2022 from https://phys.org/news/2022-10-mouse-embryo-stem -cells-mammalian .html

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Creating a mouse embryo from stem cells to learn more about the mammalian development process

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