Differentiation of SH-SY5Y Cells into Cortical Neuron-like Cells for Tauopathy Modeling and Seeding Assays

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F25%3A73631650" target="_blank" >RIV/61989592:15640/25:73631650 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15110/25:73631650

Result on the web

<a href="https://link.springer.com/article/10.1007/s12035-025-05100-3" target="_blank" >https://link.springer.com/article/10.1007/s12035-025-05100-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12035-025-05100-3" target="_blank" >10.1007/s12035-025-05100-3</a>

Result language

angličtina

Original language name

Differentiation of SH-SY5Y Cells into Cortical Neuron-like Cells for Tauopathy Modeling and Seeding Assays

Original language description

SH-SY5Y cells are widely used as an in vitro neuronal model, yet reliable differentiation protocols tailored for tauopathy research remain limited. Effective differentiation is essential for studying tau aggregation, propagation, and neurodegenerative mechanisms. Here, we present an optimized two-step differentiation protocol for TauP301L-expressing SH-SY5Y cells that enhances neuronal maturation and tauopathy modeling, providing a physiologically relevant system for investigating tau seeding. SH-SY5Y cells expressing TauP301L-EGFP under an inducible system were differentiated using a two-step protocol consisting of retinoic acid (RA) for 72 h, followed by brain-derived neurotrophic factor (BDNF) and RA for 72 h. Differentiated neurons were then exposed to exogenous P301L tau peptide fibrils to assess their susceptibility to tau seeding and aggregation. Differentiation resulted in increased neurite outgrowth, cholinergic marker expression (ChAT upregulation, TH downregulation), and upregulation of the mature 2N4R tau isoform. Western blot analysis showed increased T22 and pSer262 tau immunoreactivity in seeded cells, consistent with tau conformational changes and pathological phosphorylation. These findings may reflect early stages of tau misfolding but do not confirm oligomer formation. Seeding also induced neurite remodeling, varicosity formation, and reduced neurite diameter-features consistent with tau-mediated pathology involving cytoskeletal changes, organelle accumulation, or axonal transport defects. This optimized differentiation protocol provides an experimentally tractable tauopathy model for investigating tau propagation and neuronal dysfunctions in a controlled human cell context. Compared to existing SH-SY5Y differentiation methods, our system provides faster neuronal maturation, controlled TauP301L induction, and enhanced tau isoform expression, making it a valuable platform for studying early tau misfolding events and therapeutic interventions in tauopathies.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

MOLECULAR NEUROBIOLOGY

ISSN

0893-7648

e-ISSN

1559-1182

Volume of the periodical

62

Issue of the periodical within the volume

10

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

12951-12962

UT code for WoS article

001502051500001

EID of the result in the Scopus database

2-s2.0-105007231005