非編碼核糖核酸在神經發育與退化的分子機制
研究胚胎中樞神經系統的發育與退化過程,是生命科學領域裡最富挑戰的一門顯學。胚胎神經幹細胞在發育過程中,可藉由時間及空間上的轉錄調控,來逐步調整並限制神經幹細胞的發育潛能,以確保其最後分化成何種特定的神經元或膠質細胞。
相對地,中樞神經系統也發展出一套精密的分子機制來完美控制其數以兆計的神經元或膠質細胞能彼此正常的溝通及連結。近年來的研究顯示,微型核糖核酸(microRNA,miRNA)和大片段非編碼RNA(lncRNA,long non-coding RNA)在神經發育的過程中,可能會扮演微調修飾後基因轉錄以及表觀遺傳記憶調節的角色。
人類完整轉錄體裡至少含有超過一半以上的ncRNAs 並且會特異性的在中樞神經系統裡表達。有趣的是,到目前為止,只有極少數的ncRNA 被鑑定出來會參與神經發育的基因調控。ncRNA 在胚胎神經系統發育和退化的角色,仍處於混沌不明的狀況。因此,我們目前的研究著重於以下三個方面:
- ncRNA 在脊髓發育及運動神經元的分化過程中所扮演的角色。
- ncRNA 如何確立成熟個體各種運動神經迴路的連結和調控。
- 利用胚胎幹細胞及誘導性多潛能幹細胞(Induced pluripotent stem cells,iPSCs)的分化技術來研究運動神經元退化性疾病的致病機轉,如「脊髓性肌肉萎縮症」及「肌萎縮性側索硬化症」等。我們冀望能藉此研究開發新的治療契機。

- PDF, 2007-2012, Dept. Pathol. Cell Biol.,
Columbia Univ., USA
- Ph.D., 2006, Gurdon Inst., Univ.
Cambridge, UK
- MS, 1999, Inst. Biochem. Sci., Natl.
Taiwan Univ.
- BS, 1997, Dept. Chemistry, Natl.
Chung Cheng Univ.
- 2021~2023, Academia Sinica Presidential Scholars Program (中研院特優學術研究獎)
- 2020~2025, MOST Frontier Science Research Program (科技部尖端研究計畫)
- 2020, MOST Outstanding Research Award (科技部傑出研究獎)
- 2019, Outstanding Alumni Award of National Chung Cheng University (國立中正大學傑出校友)
- 2019, The 15th TienTe Lee Award-Young Scientists, TienTe Lee Biomedical Foundation (李天德青年醫藥獎)
- 2018, Academia Sinica Junior Research Investigators Award (年輕學者著作獎)
- 2018~2022, Academia Sinica Career Development Award (前瞻計畫)
- 2012~2015, Taiwan National Science Council Talented Investigator Fellowship (延攬人才)
- 2012~2014, Academia Sinica Investigator Fellowship (新聘學術獎)
- 2008~2009, Taiwan National Science Council Postdoctoral Fellowship
- Liau ES, Jin SQ, Chen YC, Liu WS, Calon M, Nedelec S, Nie Q*, Chen JA* (2022) Single-cell transcriptomic analysis unveils the diversity within mammalian spinal motor neurons. Nature Communications (accepted).
- Li CJ, Liau ES, Lee YH, Huang YZ, Liu ZY, Willems A, Garside V, McGlinn E, Chen JA*, Tian H* (2021) MicroRNA Governs Bistable Cell Differentiation and Lineage Segregation via a Noncanonical Feedback. Mol Syst Biol 17:e9945 (Cover featured article).
This paper is highlighted in the news of UTK.
- Chang SH, Su YC, Chang M, Chen JA*. (2021) MicroRNAs Mediate Precise Control of Spinal Interneuron Populations to Exert Delicate Sensory-to-motor Outputs. eLife (DOI: 10.7554/eLife.63768).
This article is selected as a showcase for featured eLife Science Digests, and the “Biomedical Picture of the Day” by MRC UK.
- Tung YT*, Peng KC, Chen, YC, Yen YP, Chang M, Thams S, Chen JA*. (2019) Mir-17~92 Confers Motor Neuron Subtype Differential Resistance to ALS-Associated Degeneration. Cell Stem Cell Aug 1;25(2):193-209 (Cover featured article).
This article has been recommended by F1000 by Andrew Yoo: 2019.This article is highlighted by Academi a Sinica (English) (Chinese). The Academia Sinica Facebook. It is also featured in a series of newspapers, inc LibertyTimes, UDN, ChinaTimes, etc., reported by international media: BioArt, Taipei Times, BioCentury, Asia Pacific Biotech News.
- Yen YP, Hsieh WF, Tsia YY, Lu YL, Liau ES ,Hsu HC, Chen YC, Liu TC, Chang M, Li J, Lin SP*, Hung JH*, Chen JA*. (2018) Dlk1-Dio3 Locus-Derived LncRNAs Perpetuate Postmitotic Motor Neuron Cell Fate and Subtype Identity. eLife (DOI: 10.7554/eLife.38080).
This article is selected as a showcase for featured eLife Science Digests. and the “Biomedical Picture of the Day” by MRC UK.
- Liau ES, Yen YP, Chen JA*. (2018) Visualization of Motor Axon Navigation and Quantification of Axon Arborization In Mouse Embryos Using Light Sheet Fluorescence Microscopy. J. Vis. Exp. (135), e57546, doi:10.3791/57546.
- Li CJ, Hong T, Tung YT, Yen YP, Hsu HC, Lu YL, Chang M, Nie Q*, Chen JA*. (2017) MicroRNA filters Hox temporal transcription noise to confer boundary formation in the spinal cord. Nature Communications 8. Article number: 14685 (2017).
This article is highlighted by Academia Sinica (English)(Chinese), and on the Academia Sinica Facebook. It has also been featured in Asia Pacific Biotech News.
- Tung YT, Lu YL, Peng KC, Yen YP, Chang M, Li J, Jung H, Thams S, Huang YP, Hung JH, Chen JA*. (2015) Mir-17∼92 Governs Motor Neuron Subtype Survival by Mediating Nuclear PTEN. Cell Reports. 2015 May 20. 10.1016/j.celrep.2015.04.050. (Cover featured article).
This article has been highlighted by Science Signaling Editor’s Choice, Alzforum.org, The ALS Forum, and PanScience (泛科學).
- Anderegg A, Lin H-P, Chen J-A, Caronia-Brown G, Cherepanova N, et al. (2013) An Lmx1b-miR135a2 Regulatory Circuit Modulates Wnt1/Wnt Signaling and Determines the Size of the Midbrain Dopaminergic Progenitor Pool. PLoS Genetics 9(12): e1003973. doi:10.1371/journal.pgen.1003973.
REVIEWS AND BOOKS
- Yen YP* & Chen JA* (2021). The m6A epitranscriptome on Neural Development and Degeneration. Journal of Biomedical Science 28; Article number: 40.
- Chen KW* & Chen JA*. (2020). Functional Roles of Long Non-coding RNAs in Motor Neuron Development and Disease. Journal of Biomedical Science 27; Article number: 38.
- Chen TH* & Chen JA*. (2019). Multifaceted Roles of MicroRNAs: From Motor Neuron Generation in Embryos to Degeneration in Spinal Muscular Atrophy. eLife 2019;8:e50848.
- Chen JA & Conn S. (2017). Canonical mRNA is the Exception rather than the Rule. Genome Biology 18:133.