論文 - 詳細
| RRC ID | 72193 |
|---|---|
| 著者 | Morimoto Y, Tokumitsu A, Sone T, Hirota Y, Tamura R, Sakamoto A, Nakajima K, Toda M, Kawakami Y, Okano H, Ohta S. |
| タイトル | TPT1 Supports Proliferation of Neural Stem/Progenitor Cells and Brain Tumor Initiating Cells Regulated by Macrophage Migration Inhibitory Factor (MIF). |
| ジャーナル | Neurochem Res |
| Abstract |
One of the key areas in stem cell research is the identification of factors capable of promoting the expansion of Neural Stem Cell/Progenitor Cells (NSPCs) and understanding their molecular mechanisms for future use in clinical settings. We previously identified Macrophage Migration Inhibitory Factor (MIF) as a novel factor that can support the proliferation and/or survival of NSPCs based on in vitro functional cloning strategy and revealed that MIF can support the proliferation of human brain tumor-initiating cells (BTICs). However, the detailed downstream signaling for the functions has largely remained unknown. Thus, in the present study, we newly identified translationally-controlled tumor protein-1 (TPT1), which is expressed in the ventricular zone of mouse embryonic brain, as a downstream target of MIF signaling in mouse and human NSPCs and human BTICs. Using gene manipulation (over or downregulation of TPT1) techniques including CRISPR/Cas9-mediated heterozygous gene disruption showed that TPT1 contributed to the regulation of cell proliferation/survival in mouse NSPCs, human embryonic stem cell (hESC) derived-NSPCs, human-induced pluripotent stem cells (hiPSCs) derived-NSPCs and BTICs. Furthermore, gene silencing of TPT1 caused defects in neuronal differentiation in the NSPCs in vitro. We also identified the MIF-CHD7-TPT1-SMO signaling axis in regulating hESC-NSPCs and BTICs proliferation. Intriguingly, TPT1suppressed the miR-338 gene, which targets SMO in hESC-NSPCs and BTICs. Finally, mice with implanted BTICs infected with lentivirus-TPT1 shRNA showed a longer overall survival than control. These results also open up new avenues for the development of glioma therapies based on the TPT1 signaling pathway. |
| 巻・号 | 47(9) |
| ページ | 2741-2756 |
| 公開日 | 2022-9-1 |
| DOI | 10.1007/s11064-022-03629-6 |
| PII | 10.1007/s11064-022-03629-6 |
| PMID | 35622214 |
| MeSH | Animals Brain / metabolism Cell Proliferation / physiology Humans Intramolecular Oxidoreductases Macrophage Migration-Inhibitory Factors* / genetics Macrophage Migration-Inhibitory Factors* / metabolism Mice MicroRNAs / metabolism Neoplasm Proteins / metabolism Neoplastic Stem Cells* / metabolism Neural Stem Cells* / metabolism Tumor Protein, Translationally-Controlled 1* / genetics |
| IF | 3.038 |
| 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 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 201B7(HPS0063) |