The Experts below are selected from a list of 72 Experts worldwide ranked by ideXlab platform

Norbert Perrimon - One of the best experts on this subject based on the ideXlab platform.

  • mechanical regulatIon of stem cell differentiatIon by the stretch activated piezo Channel
    Nature, 2018
    Co-Authors: Li He, Guangwei Si, Aravinthan D T Samuel, Jiuhong Huang, Norbert Perrimon
    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.

Jean-yves Le Guennec - One of the best experts on this subject based on the ideXlab platform.

  • The Stretch-Activated Ion Channel blocker gadolinium also blocks L-type calcium Channels in isolated ventricular myocytes of the guinea-pig.
    Biochimica et biophysica acta, 1994
    Co-Authors: Alain Lacampagne, François Gannier, J Argibay, D Garnier, Jean-yves Le Guennec
    Abstract:

    We show that gadolinium (Gd3+) is a potent calcium Channel blocker in guinea-pig isolated ventricular myocytes. A dose-dependent inhibitIon of ICaL was found with an EC50 of 1.4 microM and a complete inhibitIon at 10 microM Gd3+. When compared with Cd2+, it appeared that the blockade of ICaL is a complex phenomenon probably involving more than one site of interactIon (a Hill coefficient of 1.6 was found for Gd3+ vs. 1.0 for Cd2+). It is concluded that Gd3+ Ions completely block ICaL at concentratIons used to block Stretch-Activated Channels (SAC), rendering its use as a specific SAC inhibitor problematic.

Francesco Tombola - One of the best experts on this subject based on the ideXlab platform.

  • stretch activated Ion Channel piezo1 directs lineage choice in human neural stem cells
    Proceedings of the National Academy of Sciences of the United States of America, 2014
    Co-Authors: Medha M Pathak, Jamison L Nourse, Truc T Tran, Jennifer Hwe, Janahan Arulmoli, Elena Bernardis, Lisa A Flanagan, Francesco Tombola
    Abstract:

    Neural stem cells are multipotent cells with the ability to differentiate into neurons, astrocytes, and oligodendrocytes. Lineage specificatIon is strongly sensitive to the mechanical properties of the cellular environment. However, molecular pathways transducing matrix mechanical cues to intracellular signaling pathways linked to lineage specificatIon remain unclear. We found that the mechanically gated Ion Channel Piezo1 is expressed by brain-derived human neural stem/progenitor cells and is responsible for a mechanically induced Ionic current. Piezo1 activity triggered by tractIon forces elicited influx of Ca(2+), a known modulator of differentiatIon, in a substrate-stiffness-dependent manner. InhibitIon of Channel activity by the pharmacological inhibitor GsMTx-4 or by siRNA-mediated Piezo1 knockdown suppressed neurogenesis and enhanced astrogenesis. Piezo1 knockdown also reduced the nuclear localizatIon of the mechanoreactive transcriptIonal coactivator Yes-associated protein. We propose that the mechanically gated Ion Channel Piezo1 is an important determinant of mechanosensitive lineage choice in neural stem cells and may play similar roles in other multipotent stem cells.

Li He - One of the best experts on this subject based on the ideXlab platform.

  • mechanical regulatIon of stem cell differentiatIon by the stretch activated piezo Channel
    Nature, 2018
    Co-Authors: Li He, Guangwei Si, Aravinthan D T Samuel, Jiuhong Huang, Norbert Perrimon
    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.

Patrick J. Prendergast - One of the best experts on this subject based on the ideXlab platform.

  • Involvement of Stretch-Activated Ion Channels in strain-regulated glycosaminoglycan synthesis in mesenchymal stem cell-seeded 3D scaffolds
    Journal of biomechanics, 2008
    Co-Authors: Louise A. Mcmahon, Veronica A. Campbell, Patrick J. Prendergast
    Abstract:

    The objective of this study was to determine if cyclic tensile strain would regulate the rate of glycosaminoglycan synthesis via Stretch-Activated Ion Channels in adult mesenchymal stem cells seeded in a collagen type I-glycosaminoglycan scaffold and treated with TGF-beta1. The applicatIon of 10% cyclic tensile loading at 1Hz for 7 days significantly increased the rate of glycosaminoglycan synthesis, as assessed using [(35)S] sulphate incorporatIon. This increase was attenuated in the presence of a Stretch-Activated Ion Channel inhibitor (10microM gadolinium chloride) demonstrating the involvement, in part, of these Ion Channels in the mechanotransductIon pathway that couples cyclic tensile loading to matrix synthesis.