| 研究課題/領域番号 |
23KJ1627
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| 研究種目 |
特別研究員奨励費
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| 配分区分 | 基金 |
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| 応募区分 | 国内 |
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| 審査区分 |
小区分42030:動物生命科学関連
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| 研究機関 | 広島大学 |
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研究代表者 |
AN Boyang 広島大学, 統合生命科学研究科, 特別研究員(DC2)
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| 研究期間 (年度) |
2023-04-25 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
2,000千円 (直接経費: 2,000千円)
2024年度: 1,000千円 (直接経費: 1,000千円)
2023年度: 1,000千円 (直接経費: 1,000千円)
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| キーワード | cortical development / neural progenitor cells / proliferation |
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| 研究開始時の研究の概要 |
Expansion of the brain neocortex distinguishes human from other animals. A set of human-specific genes have been proven to promote cortical expansion. Since cortical expansion emerges progressively during evolution, certain conserved genes should also be involved in this process by finely tuning their expression levels. I hypothesize that species-specific non-coding RNAs regulate cell-type-dependent transcription levels of conserved neighboring genes. In particular, I will focus on evaluating the biological significance of human-specific promoter non-coding RNAs regulating cortical expansion.
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| 研究実績の概要 |
Using public RNA-seq data, candidate genes that are highly expressed in human neural progenitor cells (NPCs) compared with mouse were screened, and human-specific pancRNAs were found near the promoters of these genes. Finally the most interesting gene TMEM25 was identified. knockdown of TMEM25 significantly inhibited human NPC proliferation. Furthermore, when TMEM25 was overexpressed in mouse brain using electroporation, it promoted the generation of basal radial glia in the human subventricular zone to increase the number of upper layer neurons in vivo. Conversely, knockdown of TMEM25 in human NPCs compromised the effects of extracellular signals, resulting in cell cycle inhibition through Akt repression, as revealed by RNA-seq analysis and pharmacological assays (FEBS letters, 2023).
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
According to the research plan, I will screen out several important pancRNA-partnered genes that can affect cortical development. In the last year, I have elucidated the mechanism of TMEM25 regulating cortical expansion and successfully published it in FEBS letters. Thus, this research is progressing smoothly.
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| 今後の研究の推進方策 |
In the future, I will elucidate the mechanism by which another important gene X affects the cortical development. I have found that it promoted the proliferation of basal progenitors and produced a sulcus gyrus-like structure in the mouse cortex. Because gene X is associated with exosome, I speculated that gene X affects neurogenesis by regulating exosomes. To test this hypothesis, I will extract exosome secreted from normal human NPCs and gene X-overexpressing NPCs to analyze the difference of miRNA profile and proteome to elucidate the molecular mechanism of gene X affecting neurogenesis.
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