Evidence map›Paper›PMID 25349416›Full record

Trial reportProceedings of the National Academy of Sciences of the United States of America2014

Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells.

Medha M Pathak, Jamison L Nourse, Truc Tran, Jennifer Hwe, Janahan Arulmoli, Dai Trang T Le, Elena Bernardis, Lisa A Flanagan, Francesco Tombola

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 396 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
396citing papers in PubMed, 1 pooled it
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

396 citing papers in PubMed, 1 synthesis or guideline pooled it, 632 citations in OpenAlex.

  1. Pooled it
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  13. Biophysics of lumen morphogenesis.Development (Cambridge, England) · 2026
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336 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Medha M PathakDepartments of Physiology and Biophysics, medhap@uci.edu ftombola@uci.edu.
Jamison L NourseNeurology, and Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697; and.
Truc TranDepartments of Physiology and Biophysics.
Jennifer HweDepartments of Physiology and Biophysics.
Janahan ArulmoliSue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697; and Biomedical Engineering and.
Dai Trang T LeDepartments of Physiology and Biophysics.
Elena BernardisSection of Dermatology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Lisa A FlanaganNeurology, and Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697; and Biomedical Engineering and.
Francesco TombolaDepartments of Physiology and Biophysics, medhap@uci.edu ftombola@uci.edu.
University of California, Irvine · USChildren's Hospital of Philadelphia · USNeurology, Inc · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Institute for Clinical and Translational ScienceUL1TR000153 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M · 2012 to 2015
$12.1M
Mechanisms of Permeation and Gating of Voltage-Sensing DomainsR01GM098973 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI TOMBOLA, FRANCESCO · 2011 to 2025
$4.5M
Training Program in Stem Cell Translational Medicine for Neurological DisordersT32NS082174 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PETER John DONOVAN, Leslie Michels Thompson · 2013 to 2026
$3.3M
NCATS NIH HHS UL1 TR000153NCI NIH HHS CA-62203NCI NIH HHS P30 CA062203NIGMS NIH HHS GM098973NIGMS NIH HHS R01 GM098973
6 · The paper itself

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.

Indexed as

Calcium SignalingCell DifferentiationCells, CulturedFemaleGene Knockdown TechniquesHumansIon Channel GatingIon ChannelsMaleMechanotransduction, CellularMultipotent Stem CellsNeural Stem CellsNeurogenesisIon ChannelsPIEZO1 protein, humanblebbistatincalcium signalingmatrix mechanicsmyosin IIYap/Taz

Identifiers

PMID25349416
PMCPMC4234578
OpenAlexW1979069664

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.