Chen, Jun-An
Non-coding RNA Function during Motor Neuron Development and Degeneration
The focus of research in our laboratory is to elucidate how neurons establish individual identity in the developing nervous system and why only specific neuron subtypes are vulnerable in the neurodegenerative diseases. We tackle these questions via studying non-coding RNAs and their roles in motor neuron generation and degeneration.
I. MicroRNA and spinal cord patterning
Neural patterning relies on transcriptional cross-repressive interactions that ensure unequivocal assignment of neural progenitor identity to proliferating cells. We have shown previously that a specific miRNA mir-17-3p participates in Olig2/Irx3 bistable loop to carve pMN/p2 boundary. Yet if other miRNAs might regulate the expression of transcription factor to fine tune dorso-ventral pattering of the spinal cord is still unclear. In addition, the recent studies reveal that with cross-repressive interaction between pairs of Hox family proteins, motor neurons acquire subtype identities along the rostrocaudal axis. We are interested in examining if any miRNA helps to shape the boundary of motor columns. By taking advantage of the power to differentiate ES derived motor neurons in ample quantity and the ease to do genetic manipulation in mouse embryos, we are probing the global functions of miRNAs and their roles in pattering of the spinal cord.
II. Apply ncRNAs to differentiate motor neuron subtypes from ES cells
Embryonic stem cells are regarded as the Holy Grail to be ultimately applied to incurable neurodegenerative diseases such as amyotrophic lateral sclerosis and Parkinson's disease. The first step towards this goal is to establish a robust protocol to get homogenous quantity of pure neuron subtypes affected in these diseases. With the identification of non-coding RNAs in each motor neuron subtype, we hope to incorporate these functional ncRNAs and establish an enhanced ES derived motor neuron method. Finally, we are also collaborating with several international laboratories to study potential non coding RNA pathology in spinal muscular atrophy and amyotrophic lateral sclerosis by mouse ES cell differentiation approach.
PATENT AND TECHNOLGY TRANSFER
- MiR-17~92 as therapeutic or diagnostic target of motor neuron (mn) degeneration diseases. USA provisional patent (application no 62/652,127) (PCT/US19/25406).
REVIEWS AND BOOKS
- Chen JA & Conn S. (2017). Canonical mRNA is the exception, rather than the rule. Genome Biology 18:133.
- 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.
RESEARCH PUBLICATIONS
- 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 is highlighted by Academia 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.