論文 - 詳細
| RRC ID | 85824 |
|---|---|
| 著者 | Sakakibara K, Tanaka K, Iida M, Imai Y, Okada M, Sahashi K, Hirunagi T, Maeda K, Kato R, Katsuno M. |
| タイトル | Label-free morphology-based phenotypic analysis of spinal and bulbar muscular atrophy muscle cell models. |
| ジャーナル | Dis Model Mech |
| Abstract |
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by CAG trinucleotide expansion in the androgen receptor (AR) gene. To improve the quality of in vitro cell-based assays for the evaluation of potential drug candidates for SBMA, we developed a morphology-based phenotypic analysis for a muscle cell model of SBMA that involves multiparametric morphological profiling to quantitatively assess the therapeutic effects of drugs on muscle cell phenotype. The analysis was validated using dihydrotestosterone and pioglitazone, which have been shown to exacerbate and ameliorate the pathophysiology of SBMA, respectively. Gene expression analysis revealed activation of the JNK pathway in the SBMA cells compared to the control cells. Phenotypic analysis revealed the effect of naratriptan, a JNK inhibitor, on the phenotypic changes of SBMA cells, and the results were confirmed by LDH assays. We then trained a predictive machine learning model to classify the drug responses, and it successfully discriminated between pioglitazone-type and naratriptan-type morphological profiles based on their morphological characteristics. Our morphology-based phenotypic analysis provides a noninvasive and efficient screening method to accelerate the development of therapeutics for SBMA. |
| 巻・号 | 18(6) |
| 公開日 | 2025-6-1 |
| DOI | 10.1242/dmm.052220 |
| PII | 368196 |
| PMID | 40474744 |
| PMC | PMC12233066 |
| MeSH | Animals Cell Line Cell Shape / drug effects Humans Models, Biological* Phenotype Pioglitazone / pharmacology |
| IF | 4.651 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |