Non-coding RNA Function during Neural Development,
Degeneration, and Regeneration
Our laboratory's focus is to elucidate how neurons establish individual
identity in the developing nervous system and why only specific neuron
subtypes are vulnerable to neurodegenerative diseases. We tackle these
questions by studying non-coding RNAs and their roles in motor neuron
generation and degeneration. "DNA→RNA→Protein" is the central dogma
of molecular biology, in which RNA is served as a temporary template
from interpreting genetic information to functional proteins. Surprisingly,
new sequencing technology of mammalian transcriptomes has revealed
that more than 50% of RNA transcripts do not possess protein-coding
elements, thus termed as non-coding RNAs (ncRNAs). Although ncRNAs
have been drawing increasing attention in recent years, the functions of
most non-coding RNAs are still undefined. This is mainly due to the lack
of a powerful method to systematically test their roles in a given cell type.
There are two major classes of regulatory non-coding RNAs: 1) small
RNAs such as microRNAs (miRNAs) that are participated in the repression
and fine-tuning of protein expression and 2) less well apprehended long
non-coding RNAs (lncRNAs) that are mainly shown to act as mediators for
epigenome regulation. As the developing spinal cord is arguably the best-characterized developmental process
in the embryonic central nervous system, our laboratory uses embryonic stem (ES) cells as a tool to systematically
study ncRNA functions during motor neuron differentiation. We focus on three major questions: 1. miRNA and
patterning in the developing spinal cord. 2. ncRNAs and motor neuron subtype generation and degeneration. 3.
Apply ncRNAs to differentiate motor neuron subtypes from ES cells molecular mechanism by which RNA decay
controls anaerobic cell growth.
- 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.