Andrew Yoo, Ph.D.

Associate Professor
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program
Neurosciences Program

  • 314-362-1811

  • 314-362-1814

  • 8103

  • yooa@WUSTL.EDU

  • http://yoolab.wustl.edu

  • neurogenesis, microRNA, cellular reprogramming, disease modeling, chromatin, regenerative medicine

  • Generation of human neurons by direct cell fate reprogramming and modeling late-onset neurodegenerative disorders

Research Abstract:

The general goal of our research is to understand genetic mechanisms underlying neurogenesis and develop cellular reprogramming approaches to generate human neurons by directly converting dermal fibroblasts. Our work centers around neuronal microRNAs whose ectopics expression in human fibroblasts leads to direct cell fate transition from fibroblasts to neurons. By employing synergistic activity between microRNAs and transcription factors, my lab generates discrete subtypes of neurons and employ directly converted neurons to model and study adult-onset neurodegenerative disorders including Huntington`s disease and Alzheimer`s disease. combining specification of cell fates. We are particularly interested in the process of neurogenesis mediated by small non-coding RNA molecules, microRNAs that control the activity of chromatin remodeling complexes during neural development. In addition, we recently discovered that two brain-enriched microRNAs, miR-9/9* and miR-124, are neurogenic molecules that could promote direct conversion (reprogramming) of human fibroblasts into neurons when ectopically expressed. Also, my lab uses interdisciplinary approaches (molecular genetics, genomics, and biochemistry) to understand how microRNAs affect chromatin landscape and promote the neuronal identity.

Selected Publications:

Lee, S.W., Oh, Y.M., Lu, Y.L., Kim, W.K., Yoo, A.S. (2018). MicroRNAs Overcome Cell Fate Barrier by Reducing EZH2-Controlled REST Stability during Neuronal Conversion of Human Adult Fibroblasts. Developmental Cell 46(1):73-84.e7. doi: 10.1016/j.devcel.2018.06.007.

McCoy, M.J.^, Paul, A.J.^, Victor, M.B., Richner, M., Gabel, H.W., Gong, H., Yoo, A.S.*, Ahn, T.H.* (2018). LONGO: an R package for interactive gene length dependent analysis for neuronal identity. Bioinformatics 34(13):i422-i428. doi: 10.1093/bioinformatics/bty243. *: co-corresponding authors, ^: co-first authors

Victor, M.B., Richner, M., Olsen, H.E., Lee, S.W., Monteys, A.M., Ma, C., Huh, C.J., Zhang, B., Davidson, B.L., Yang, X.W., Yoo, A.S. (2018). Striatal neurons directly converted from Huntington’s disease patient fibroblasts recapitulate age-associated disease phenotypes. Nature Neuroscience 3:341-352 doi: 10.1038/s41593-018-0075-7.

Abernathy, D.G.*, Kim, W.K.*, McCoy, M.J.*, Lake, A.M., Ouwenga, R., Lee, S.W., Xing, X., Li, D., Lee, H.J., Heuckeroth, R.O., Dougherty, J.D., Wang, T., Yoo, A.S. (2017). MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts. Cell Stem Cell 21, 332-348. *: co-first authors

Huh, C.J., Zhang, B, Victor, M.B., Dahiya, S., Batista, L.F., Horvath, S., and Yoo, A.S. (2016). Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts. eLife 5:e18648.

Richner, M.*, Victor, M.B.*, Liu, Y., Abernathy, D., and Yoo, A.S. (2015). MicroRNA-based conversion of human fibroblasts into striatal medium spiny neurons. Nature Protocols 10, 1543-1555. *: co-first authors

Victor, M.B.*, Richner, M.*, Hermanstyne, T.O., Ransdell, J.O., Sobieski, C., Deng, P.Y., Klyachko, V.A., Nerbonne, J.M., Yoo, A.S. (2014). Generation of human striatal neurons by microRNA-dependent direct conversion of fibroblasts. Neuron 84, 311-323. *: co-first authors [Featured in Neuron Best of 2014-2015]

Yoo, A.S.*, Sun, A.X., Li, L., Shcheglovitov, A., Portmann, T., Li, Y., Lee-Messer, C., Dolmetsch, R.E., Tsien, R.W., and Crabtree, G.R.* (2011). MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476, 228-231. *: corresponding authors

Yoo, A.S., Staahl, B.T., Chen, L., and Crabtree, G.R. (2009). MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature 460, 642-646.

Yoo, A.S., and Greenwald, I. (2005). LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. Science 310, 1330-1333.

Last Updated: 7/27/2018 11:24:45 AM

An example of human neurons converted from dermal fibroblasts
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