2023 Fiscal Year Research-status Report
Impacts of Species-dependent Long Non-coding RNA Expression on Formation of Phenotypic Diversity in Mammalian Cerebral Cortex
| Project/Area Number |
23KJ1627
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| Research Institution | Hiroshima University |
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Principal Investigator |
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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| Project Period (FY) |
2023-04-25 – 2025-03-31
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| Keywords | cortical development / neural progenitor cells / proliferation |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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