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Tissue regeneration in the gut visible for first time


Researchers from Utrecht University, Hubrecht Institute and UMC Utrecht have succeeded in making the mechanisms that regulate tissue regeneration in the gut visible. This discovery provides new insights into how stem cells function and offers tie-ins for future research into regenerative medicine and treatments for cancer. The research results are being published this week in Nature.

Darm-organoidMany of our organs have small populations of stem cells that are used to repair wear and tear to tissues by producing a supply of new young cells through cell division. These new cells then adopt appropriate specializations in accordance with the tasks of the tissue in question. The life cycle from newly born to specialized cell is coordinated precisely through the emission of protein signals by surrounding cells. A signal gradient is formed through which the cells receive instructions as to where they should be in the tissue and what task they should perform. Cells that receive the highest concentration of signals will retain stem cell properties, whereas those that receive lower concentrations will specialize.

Hans Clevers, professor of Molecular genetics at Utrecht University, and Madelon Maurice of UMC Utrecht led a team that discovered how one of the main growth signals for stem cells, the Wnt protein, forms a gradient in gut tissue. A small genetic modification has now made this protein-in-action visible for the first time.

The results show that the Wnt proteins are largely produced by special caretaker cells located close to the stem cells. This creates an optimal local environment (the “niche”) in which the stem cells thrive. The Wnt proteins accumulate on the outside of the caretaker cell and are transferred to the stem cells directly through cell-to-cell contact. As the cells in the niche divide, the accumulated Wnt proteins become increasingly thinned out, creating a gradient.

This gradient of Wnt proteins formed plays an essential role in accurately regulating the creation and destruction of cells in the tissue. Disruptions to this balance can have serious consequences: insufficient cell division leads to a loss of tissue (degeneration) and excessive cell division leads to cancer. The insights generated by Clevers and Maurice are important for developing methods to stimulate stem cell activities during tissue regeneration or inhibiting them in the event of cancer.

Farin HF, Jordens I, Mosa M, Basak O, Korving J, Tauriello DVF, de Punder K, Angers S, Peters PJ, Maurice MM, Clevers H. Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 2016, in press.

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