Non-protein coding RNAs in neural development and neurodegenerative disease

With the current access to fully sequenced genomes and annotations, it is evident that the number of protein-coding genes cannot account for differences in complexity between organisms. Higher complexity rather appears to be due to increased transcriptional control and an expanded repertoire of non-protein coding RNAs (ncRNAs).

Our goal is to understand the roles of specific ncRNAs in neural cell specification and in neurodegeneration. To model neurodegeneration we are studying neurons differentiated from pluripotent stem cells generated from patients with familial Alzheimer’s disease. These neurons display typical signs of Alzheimer’s disease, including amyloid beta peptide pathology. Candidate ncRNAs are selected based on i) their differential expression during differentiation of mouse and human neural cells or ii) differential expression between healthy and disease neurons. Candidate ncRNAs are subjected to functional and mechanistic studies, including overexpression and knock-down studies, RNA expression profiling and RNA-protein interaction studies.
 

Keywords

ncRNA, iPS, stem cells, neurogenesis, Alzheimer's Disease

Selected publications

Andersson, T., Duckworth, J.K., Fritz, N., Lewicka, M., Södersten, E., Uhlén, P., & Hermanson, O. (2011). Noggin and Wnt3a enable BMP4-dependent differentiation of telencephalic stem cells into GluR-agonist responsive neurons.  Mol Cell Neurosci. 47(1):10-8

Andersson, T., Rahman, S., Sansom, S.N., Alsiö, J.M., Kaneda, M., Smith, J., O'Carroll, D., Tarakhovsky, A., & Livesey, F.J. (2010). Reversible block of mouse neural stem cell differentiation in the absence of dicer and microRNAs. PLoS One. 5(10):e13453

Andersson, T., Södersten, E., Duckworth, J.K., Cascante, A., Fritz, N., Sacchetti, P., Cervenka, I., Bryja, V., & Hermanson, O. (2009). CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells. J Biol Chem. 284(6):3672-81

Chung, S., Sonntag, K.C., Andersson, T., Bjorklund, L.M., Park, J.J., Kim, D.W., Kang, U.J., Isacson, O., & Kim, K.S. (2002). Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neurons. Eur J Neurosci. 16(10):1829-38

Bjorklund, L.M., Sánchez-Pernaute, R., Chung, S., Andersson, T., Chen, I.Y., McNaught, K.S., Brownell, A.L., Jenkins, B.G., Wahlestedt, C., Kim, K.S., & Isacson, O. (2002). Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci U S A. 99(4):2344-9.