Evidence map›Paper›PMID 40682198›Full record

ArticleStem cell research & therapy2025

Enhanced neuromorphogenesis of neural stem cells via the optimization of physical stimulus-responsive signaling pathways.

Youyi Tai, Natasha Brinkley, Lu Jin, Yu Wei Chang, Allen Liakhovetski, Jin Nam

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Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Youyi TaiDepartment of Bioengineering, University of California, Riverside, CA, USA.
Natasha BrinkleyDepartment of Bioengineering, University of California, Riverside, CA, USA.
Lu JinDepartment of Bioengineering, University of California, Riverside, CA, USA.
Yu Wei ChangDepartment of Bioengineering, University of California, Riverside, CA, USA.
Allen LiakhovetskiDepartment of Bioengineering, University of California, Riverside, CA, USA.
Jin NamDepartment of Bioengineering, University of California, Riverside, CA, USA. jnam@engr.ucr.edu.ORCID http://orcid.org/0000-0001-5117-8958

Funding

California Institute for Regenerative Medicine EDUC4-12752National Science Foundation CBET-1805975
6 · The paper itself

Abstract

backgroundNeural stem cells hold significant promise for developing in vitro nerve models due to their capacity to differentiate into diverse neural cell types. While traditional biochemical approaches often restrict differentiation to a single phenotype, limiting the ability to study critical neuron-glia interactions, physical stimuli have been explored due to their capacity to drive multi-phenotypic differentiation of neural stem cells. However, underlying molecular mechanisms mediating the physical stimulation-induced neural stem cell differentiation, with an emphasis on electrical stimulation and mechanical stimulation, remain inadequately explored, hindering the comprehensive optimization and application of physical stimulation for enhanced neuromorphogenesis.

methodsIn this study, we explored the signaling pathways driving mechano-electrical stimulation-induced multi-phenotypic differentiation of NSCs using a piezoelectric platform with signaling inhibitors. The signaling knowledge was then used to further enhance the neuromorphogenesis by employing signal activator/inhibitor in combination with mechano-electrical stimulation.

resultsWe discovered that electrical stimulation promotes the neuronal differentiation of NSCs via Wnt signaling through the TRPC1 channel, while mechanical stimulation activates the TRPV4-RhoA/ROCK axis, inducing astrocytic and oligodendrocytic differentiation via JAK/Stat3 and Shh/Gli1 pathways, respectively. Targeted modulation of these pathways under mechano-electrical stimulation further enhanced neuromorphogenesis, including improved neurite outgrowth, synaptic interactions, and myelin maturation.

conclusionsThis study systematically uncovered the signaling cascades that mediate the mechano-electrical stimulation-induced multi-phenotypic differentiation of neural stem cells towards neurons and glial cells, which were separately mediated by electrical stimulation and mechanical stimulation, respectively, through independent signaling cascades. The combination of physical stimulation with biochemical factors to modulate those signaling pathways further enhanced neuromorphogenesis, offering a reliable and robust strategy to develop fully functional neural stem cell-derived in vitro nerve models.

Indexed as

Neural Stem CellsNeurogenesisSignal TransductionAnimalsCell DifferentiationCells, CulturedElectric StimulationMiceNeuronsMechano-electrical stimulationNerve tissue modelNeural stem cell differentiationNeuromorphic signaling pathway

Identifiers

PMID40682198
PMCPMC12275341

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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.