Piezo1 forms a slowly-inactivating mechanosensory channel in mouse embryonic stem cells
Abstract
Piezo1 is a mechanosensitive (MS) ion channel with characteristic fast-inactivation kinetics. We found a slowly-inactivating MS current in mouse embryonic stem (mES) cells and characterized it throughout their differentiation into motor-neurons to investigate its components. MS currents were large and slowly-inactivating in the stem-cell stage, and became smaller and faster-inactivating throughout the differentiation. We found that Piezo1 is expressed in mES cells, and its knockout abolishes MS currents, indicating that the slowly-inactivating current in mES cells is carried by Piezo1. To further investigate its slow inactivation in these cells, we cloned Piezo1 cDNA from mES cells and found that it displays fast-inactivation kinetics in heterologous expression, indicating that sources of modulation other than the aminoacid sequence determine its slow kinetics in mES cells. Finally, we report that Piezo1 knockout ES cells showed a reduced rate of proliferation but no significant differences in other markers of pluripotency and differentiation.
Data availability
Sequencing data have been deposited in GEO under accession number GSE106526. Source dat files have been provided for figures 1, 2, 4, 5, and 6, and source data for figure 7 is included as supporting file.
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High-throughput RNA seq data of mouse embryonic stem cells and intermediate states throughout their differentiation into motor neuronsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106526).
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Josefina Inés del Mármol
- Roderick MacKinnon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kenton Jon Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
Version history
- Received: October 26, 2017
- Accepted: August 21, 2018
- Accepted Manuscript published: August 22, 2018 (version 1)
- Version of Record published: September 7, 2018 (version 2)
Copyright
© 2018, del Mármol et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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