Evidence map›Paper›PMID 21956892›Full record

ArticleStem cells (Dayton, Ohio)2011

Rho GTPases mediate the mechanosensitive lineage commitment of neural stem cells.

Albert J Keung, Elena M de Juan-Pardo, David V Schaffer, Sanjay Kumar

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed
–field-weighted citation impact, top 94% 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

116 citing papers in PubMed, 2 citations in OpenAlex.

  1. 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
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  16. Substrate stress relaxation regulates neural stem cell fate commitment.Proceedings of the National Academy of Sciences of the United States of America · 2024
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56 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

4 authors at 1 institution in 2 countries.

Albert J KeungDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, California 94720-3220, USA.
Elena M de Juan-Pardo
David V Schaffer
Sanjay Kumar
University of California, Berkeley · US

Funding

Cellular mechanobiology: Biophysics and therapeuticsDP2OD004213 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI KUMAR, SANJAY · 2008 to 2008
$2.3M
Bioactive Materials for Stem Cell ControlR21EB007295 · NIBIB · RENSSELAER POLYTECHNIC INSTITUTE · PI KANE, RAVI S. · 2008 to 2009
$446k
Molecular Engineering of Bioactive HydrogelsR21DE018044 · NIDCR · UNIVERSITY OF CALIFORNIA BERKELEY · PI SCHAFFER, DAVID V · 2008 to 2009
$382k
NIBIB NIH HHS EB007295NIBIB NIH HHS R21 EB007295NIDCR NIH HHS DE018044NIDCR NIH HHS R21 DE018044NIH HHS 1DP2OD004213NIH HHS DP2 OD004213
6 · The paper itself

Abstract

Adult neural stem cells (NSCs) play important roles in learning and memory and are negatively impacted by neurological disease. It is known that biochemical and genetic factors regulate self-renewal and differentiation, and it has recently been suggested that mechanical and solid-state cues, such as extracellular matrix (ECM) stiffness, can also regulate the functions of NSCs and other stem cell types. However, relatively little is known of the molecular mechanisms through which stem cells transduce mechanical inputs into fate decisions, the extent to which mechanical inputs instruct fate decisions versus select for or against lineage-committed blast populations, or the in vivo relevance of mechanotransductive signaling molecules in native stem cell niches. Here we demonstrate that ECM-derived mechanical signals act through Rho GTPases to activate the cellular contractility machinery in a key early window during differentiation to regulate NSC lineage commitment. Furthermore, culturing NSCs on increasingly stiff ECMs enhances RhoA and Cdc42 activation, increases NSC stiffness, and suppresses neurogenesis. Likewise, inhibiting RhoA and Cdc42 or downstream regulators of cellular contractility rescues NSCs from stiff matrix- and Rho GTPase-induced neurosuppression. Importantly, Rho GTPase expression and ECM stiffness do not alter proliferation or apoptosis rates indicating that an instructive rather than selective mechanism modulates lineage distributions. Finally, in the adult brain, RhoA activation in hippocampal progenitors suppresses neurogenesis, analogous to its effect in vitro. These results establish Rho GTPase-based mechanotransduction and cellular stiffness as biophysical regulators of NSC fate in vitro and RhoA as an important regulatory protein in the hippocampal stem cell niche.

Indexed as

AnimalsApoptosiscdc42 GTP-Binding ProteinCell DifferentiationCell ProliferationCells, CulturedExtracellular MatrixFemaleFluorescent Antibody TechniqueMechanotransduction, CellularMicroscopy, Atomic ForceNeural Stem CellsNeurogenesisRatsRats, Inbred F344rhoA GTP-Binding Proteincdc42 GTP-Binding ProteinrhoA GTP-Binding Proteinrho GTP-Binding Proteins

Identifiers

PMID21956892
PMCPMC5990277
OpenAlexW1595190660

What OpenQuestion holds

Textmetadata
LicenceTDM
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.