Regulation of cell polarity by EGF signaling controls both organ architecture and cell fate
Scientists at DanStem discovered that cells’ sense of direction (cell polarity) determines their destiny. By discovering the signals that control cell polarity in the developing organism, scientists can now mimic it in a test tube and control the fate of human stem cells. The results accelerate the efforts to generate specialized cells, e.g. insulin-producing beta cells, from stem cells to treat and maybe even cure chronic diseases
The paper, published in Nature Cell Biology, by the Semb Group at DanStem, shows that cell polarity (the cell’s ability to sense what is up and down) in progenitor cells not only contribute to the architecture and shape of organs, e.g. tubular systems, but also governs the fate progenitor cells.
Video: 3D volume rendering of two endocrine progenitor cells (green membrane and red nuclei). The cell on the left is immature and has a larger apical domain facing the lumen of the duct (labeled in red) while the other cell has downregulated the apical domain. Embryonic mouse pancreas grown and imaged live in vitro
Major scientific findings of the paper
The scientists answer a fundamental question as to how the limited number of genes in our genome can control the large complexity of our organism. The results illustrate how genes are re-utilized in a context-dependent manner to expand their ability to control, not only one, but a many complex cellular events during organ formation.
Epidermal growth factor (EGF) signaling is identified as an essential regulator of cell polarity throughout pancreas formation to regulate tube formation (early) as well as the birth of insulin-producing beta cells (late).
The paper answers a long-sought question: how progenitors in the developing pancreas are instructed to become insulin-producing beta cells.
This discovery can be utilized to increase the efficiency and robustness of differentiating human pluripotent stem cells into insulin-producing beta cells for future cell therapy in type 1 diabetes, and deliver new general concepts for how cues from the environment instruct organ-specific multipotent progenitors into their different fates.
Löf Öhlin, Zarah, Pia Nyeng, Matthew Bechard, Katja Hess, Eric Bankaitis, Thomas U. Greiner, Jacqueline Ameri, Christopher V. Wright & Henrik Semb (2017). Context-specific regulation of apicobasal polarity by EGFR orchestrates epithelial morphogenesis and cellular fate. Nature Cell Biology, doi: 10.1038/ncb3628.
Professor Henrik Semb