NOV 08, 2017 6:00 PM PST

Utilization of Stem Cells to Crack Motor Neuron Development and Degeneration

  • Assistant Research Fellow, Institute of Molecular Biology, Academia Sinica
      The focus of research in my 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 during motor neuron generation and degeneration. My lab employs motor neurons generated from mouse and human embryonic (ES) and induced pluripotent (iPS) stem cells, as well as mouse animal models to investigate motor neuron development and disease. We have developed and generated a series of stem cells and animal models to study functions of microRNA and lncRNA by "gain-of-function" and "loss-od-function" approaches. Besides elucidating the basic molecular mechanisms underlying specification of neuronal diversity during CNS development, I apply the stem cell system to study motor neuron diseases. In particular, I am engaged in the establishment and study of patient specific iPS cell based models of Spinal Muscular Atrophy (SMA), Amyotrophic Lateral Sclerosis (ALS). iPS cell derived motor neurons are used in my lab to perform deep sequencing from healthy and ALS motor neurons and to functionally characterize non-coding RNA pathology in motor neuron. I am also a core member of Neuroscience Program and RNA program in Academia Sinica, which provides strong and solid consortium to give advices and exchange the ideas for our projects. In summary, I have multidisciplinary approaches, from in vitro stem cells to in vivo mouse models, to study motor neuron development and degeneration.


    Regulatory non coding RNAs, including microRNAs (miRNAs) and long non coding RNAs (lncRNAs), have shown to be essential for animal development and viability, yet dissecting the relevance of individual miRNA or lncRNA has been challenging for a given cell context. In addition, the role of ncRNAs for neurodegeneration is still obscure. To identify ncRNAs participated during motor neuron development and degeneration, we used human embryonic stem cell and motor neuron disease iPSCs as paradigms and robustly harnessed them into different motor neuron subtypes to perform strand specific RNA-seq and small RNA-seq simultaneously. We identified several novel MN signature miRNAs and lncRNAs, and systematically analyzed their functions by generating knockout mice. I will present the current progress of the characterization of these MN-ncRNAs by gain-of-function and loss-of-function studies. Collectively, these results will provide critical information for ncRNAs function and will fill in the information on how ncRNAs mediate MN development in vivo.

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