Institute for Stem Cell Biology and Regenerative Medicine

Marius Wernig Laboratory

“Only those who attempt the absurd can achieve the impossible.”

--Albert Einstein

neurons

Research in the Wernig Lab
Our lab is generally interested in the mechanisms that determine cell fate identity. Our focus is on epigenetic reprogramming i.e. ways to induce cell fate changes by defined factors such as the reprogramming of somatic cells into pluripotent stem (or iPS) cells. More recently, we have demonstrated that mouse fibroblasts can directly be converted to functional neuronal cells that we termed induced neuronal (iN) cells (Vierbuchen et al., 2010, Nature). The iN cells were generated through expression of the three transcription factors Ascl1, Myt1l, and Brn2. This surprising discovery opened the door to a new area of investigation. We are currently working to apply our finding to human cells, explore the molecular mechanism of the action of the three transcription factors, and determine the neuronal subtype of resulting iN cells. A long term goal is to use this method to evaluate whether iN cells can be used to model neurological diseases. In addition, the emerging iPS cell technology provides new fascinating translational applications such as patient-specific stem cell therapy or disease phenocopy through differentiation into the neural lineage. Our lab has developed new methods to generate iPS cells from human fibroblasts with defined mutations and explores various technologies to improve gene targeting in human iPS cells with a long term goal to correct disease-causing mutations. This work is made possible through a very generous CIRM grant. Another interest of the laboratory is to study self-renewal and differentiation in neural stem/progenitor cells and apply these findings to the tumor precursor cells of glioblastoma. This will shed some light into glioma generation and potentially lead to alternative treatment strategies of this devastating brain disease.

 

Lab Info
Selected Publications

Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Südhof TC, Wernig M. Induction of human neuronal cells by defined transcription factors. Nature. 2011

Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M. "Direct conversion of fibroblasts to functional neurons by defined factors." Nature 2010 Feb 25;463(7284):1035-41. Epub 2010 Jan 27.

Wernig M, Lengner CJ, Hanna J, Lodato MA, Steine E, Foreman R, Staerk J, Markoulaki S, Jaenisch R "A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types." Nat Biotechnol 2008; 26: 8: 916-24 More »

Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R "Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease." Proc Natl Acad Sci U S A 2008; 105: 15: 5856-61 More »

Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R "In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state." Nature 2007; 448: 7151: 318-24 More »

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Dr. Wernig explains how to make induced pluripotent stem cells

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