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Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel.

ABSTRACT: 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.

SUBMITTER: He L

PROVIDER: S-EPMC6101000 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel.

He Li L Si Guangwei G Huang Jiuhong J Samuel Aravinthan D T ADT Perrimon Norbert N

Nature 20180207 7694

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 ...[more]

PMID: 29414942

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Project description:Severe malocclusion can contribute to several serious dental and physical conditions, such as digestive difficulties, periodontal disease, and severe tooth decay. Orthodontic treatment is mainly used to treat malocclusion. Forces in orthodontic tooth results in bone resorption on the pressure side and bone deposition on the tension side. Osteoblasts have been considered as the key component in bone regeneration on the tension side. However, the underlying mechanisms remain unclear. In this study, we focus on how mechanical stretch regulates the osteogenesis during orthodontic treatment. Human jaw bone marrow mesenchymal stem cells (hJBMMSCs) were isolated from healthy adult donors and cultured in regular medium (control) or osteogenic medium (OS). Under OS culture, hJBMMSCs presented osteogenic differentiation potentials, as evidenced by increased mineralization, enhanced calcium deposition, and upregulated expression of osteogenesis markers (ALP, osterix, and Runx). What's more, the OS-induced osteogenesis of hJBMMSCs is associated with the dephosphorylation of IKK, activation of IKB?, and phosphorylation/nucleic accumulation of P65, which all indicated the inhibition of NF-?B activity. Overexpressing P65 in hJBMMSCs, which could constantly activate NF-?B, prevented the osteogenic differentiation in the OS. After that, we applied the Flexcell tension system, which could cause mechanical stretch on cultured hJBMMSCs to mimic the tension forces during tooth movement. Mechanical stretch resulted in 3.5-fold increase of ALP activity and 2.4-fold increase of calcium deposition after 7 days and 21 days treatment, respectively. The expression levels of ALP, Run×2, and Osterix were also significantly upregulated. In the meantime, applying mechanical stretch on OS-cultured hJBMMSCs also dramatically promoted the OS-induced osteogenesis. Both OS and mechanical stretch downregulated NF-?B activity. By overexpressing P65 in hJBMMSCs, neither OS nor mechanical stretch could induce their osteogenesis. These results indicated that, like OS induction, mechanical stretch-facilitated osteogenesis of hJBMMSCs by inhibiting NF-?B in the noninflammatory environments.

Dataset Information

Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel.

Publications

Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel.

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