Eggan Lab

2016 Sep 25

10 Years of iPSCs

Mon - Wed, Sep 25 to Sep 27, 8:00am - 6:00pm

Location: 

Claremont Hotel & Spa, 41 Tunnel Road, Berkeley, CA

*Cell Symposia* *Keynote addresses by:* /*Shinya Yamanaka*/ and /*Rudolf Jaenisc*/h In 2006, Shinya Yamanaka and Kazutoshi Takahashi reported the Nobel Prize winning discovery of induced pluripotent stem cells (iPSCs) in Cell. In the ten years that have passed since, iPSC technology has provided fundamental insights into our understanding of cell fate, mammalian development, and human disease. It has also spurred renewed interest in direct reprogramming across lineages, and this area too has flourished.

Kiskinis E, Sandoe J, Williams LA, Boulting GL, Moccia R, Wainger BJ, Han S, Peng T, Thams S, Mikkilineni S, et al. Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Cell Stem Cell. 2014;14 (6) :781-95. PMCID: PMC4653065.Abstract

Although many distinct mutations in a variety of genes are known to cause Amyotrophic Lateral Sclerosis (ALS), it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neuronal degeneration. Here, we have combined reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing to define the transcriptional and functional changes that are induced in human motor neurons by mutant SOD1. Mutant SOD1 protein induced a transcriptional signature indicative of increased oxidative stress, reduced mitochondrial function, altered subcellular transport, and activation of the ER stress and unfolded protein response pathways. Functional studies demonstrated that these pathways were perturbed in a manner dependent on the SOD1 mutation. Finally, interrogation of stem-cell-derived motor neurons produced from ALS patients harboring a repeat expansion in C9orf72 indicates that at least a subset of these changes are more broadly conserved in ALS.

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