“May the Force be with you” — Environmental signal of MECHANICAL FORCE that regulates stem cell differentiation !!

Over the past decade, advances in bioengineering have led to newly appreciated methods to study effects of mechanical force on single cells. Micrometer-scale culture systems that can subject individual cells to highly specific physical distortion have allowed scientists to demonstrate that force can modulate stem-cell behavior. Authors [see attached full-length article] combined sophisticated genetic approaches and innovative physical manipulations to inves­tigate the role of force on stem cells in the fruit fly. They make the intriguing discovery that mechanical force drives differentiation of a very specialized population of progenitor cells in the midgut of adult Drosophila melanogaster flies.

The fruit-fly midgut is equivalent to the stomach and small intestine of humans and other vertebrates (animals with a spine). All digestive organs experience physical forces that are inherent in their physiological functions: ingested food distends the gut; muscle contractions compress the gut. These forces contin­uously deform the gut’s epithelial lining. Like their mammalian counterparts, fly intestinal stem cells (ISCs) produce two major classes of cells that comprise the adult intestinal epithelium: absorptive enterocytes and secretory enteroendocrine cells. Many extrinsic signals –– including chemicals, nutrition, pathogens and cytokines –– have been shown to regulate ISC proliferation and differentiation. However, until now, whether midgut stem cells can sense biomechanical signals remained unknown.

Authors studied PiezoP-GAL4, a GAL4 transgene under control of a cloned promoter region of Piezo, expressed in a subpopulation of stem cells in the adult fly midgut. PIEZO is a cation ion channel that directly senses mechanical tension in lipid bilayers; it was initially identified in mammalian cells as a touch sensor, and was later found to be responsible for mechano-reception (able to perceive mechanical energy as a signal) in other cell types. The Drosophila genome contains a single Piezo homolog.

Authors [see attached] showed that mechanical stress regulates stem-cell differentiation in adult Drosophila midgut through the stretch-activated ion channel PIEZO. Loss of the Piezo gene lowers the generation of enteroendocrine cells in the adult midgut. Increases in cytosolic Ca2+ resemble the PIEZO overexpression phenotype, suggesting that PIEZO functions through Ca2+-signaling. Further studies suggested that Ca2+ signaling promotes stem-cell proliferation and differentiation through separate pathways. This interesting paper demonstrates the existence of a specific group of stem cells in the fly midgut that can directly sense mechanical signals through PIEZO, encoded by the fly gene, Piezo.


Nature 1 Mar 2o18; 555: 103–106 & News’N’Views pp 34–36

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