Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel. He L et al. (2018) Somatic stem cells constantly adjust their self-renewal and lineage commitment by integrating various environmental cues to maintain tissue homeostasis. Although numerous chemical and biological signals have been identified that regulate stem-cell behaviour, whether stem cells can directly sense mechanical signals in vivo remains unclear. Here we show that mechanical stress regulates stem-cell differentiation in the adult Drosophila midgut through the stretch-activated ion channel Piezo. We find that Piezo is specifically expressed in previously unidentified enteroendocrine precursor cells, which have reduced proliferation ability and are destined to become enteroendocrine cells. Loss of Piezo activity reduces the generation of enteroendocrine cells in the adult midgut. In addition, ectopic expression of Piezo in all stem cells triggers both cell proliferation and enteroendocrine cell differentiation. Both the Piezo mutant and overexpression phenotypes can be rescued by manipulation of cytosolic Ca2+levels, and increases in cytosolic Ca2+resemble the Piezo overexpression phenotype, suggesting that Piezo functions through Ca2+signalling. Further studies suggest that Ca2+signalling promotes stem-cell proliferation and differentiation through separate pathways. Finally, Piezo is required for both mechanical activation of stem cells in a gut expansion assay and the increase of cytosolic Ca2+in response to direct mechanical stimulus in a gut compression assay. Thus, our study demonstrates the existence of a specific group of stem cells in the fly midgut that can directly sense mechanical signals through Piezo.//////////////////
NCBI Summary:
The protein encoded by this gene is a mechanically-activated ion channel that links mechanical forces to biological signals. The encoded protein contains 36 transmembrane domains and functions as a homotetramer. Defects in this gene have been associated with dehydrated hereditary stomatocytosis. [provided by RefSeq, Jul 2015]
General function
Channel/transport protein
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Ovulation
Comment
Expression regulated by
LH
Comment
Goes up after hCG
Ovarian localization
Granulosa
Comment
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: C. elegans
Mutation name: type: naturally occurring fertility: subfertile Comment:Caenorhabditis elegans PIEZO channel coordinates multiple reproductive tissues to govern ovulation. Bai X et al. (2020) PIEZO1 and PIEZO2 are newly identified mechano-sensitive ion channels that exhibit a preference for calcium in response to mechanical stimuli. In this study, we discovered the vital roles of pezo-1, the sole PIEZO ortholog in C. elegans, in regulating reproduction. A number of deletion alleles as well as a putative gain-of-function mutant of PEZO-1 caused a severe reduction in brood size. In vivo observations showed that oocytes undergo a variety of transit defects as they enter and exit the spermatheca during ovulation. Post ovulation oocytes were frequently damaged during spermathecal contraction. However, the calcium signaling was not dramatically changed in the pezo-1 mutants during ovulation. Loss of PEZO-1 also revealed an inability of self-sperm to properly navigate back to the spermatheca after being pushed out of the spermatheca during ovulation. These findings suggest that PEZO-1 acts in different reproductive tissues to promote proper ovulation and fertilization in C. elegans.//////////////////