Direct generation of functional dopaminergic neurons from mouse and human fibroblasts

Massimiliano Caiazzo, Maria Teresa Dell’Anno, Elena Dvoretskova, Dejan Lazarevic, Stefano Taverna, Damiana Leo, Tatyana D. Sotnikova, Andrea Menegon, Paola Roncaglia, Giorgia Colciago, Giovanni Russo, Piero Carninci, Gianni Pezzoli, Raul R. Gainetdinov, Stefano Gustincich, Alexander Dityatev and Vania Broccoli ()
Additional contact information
Massimiliano Caiazzo: Stem Cells and Neurogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy
Maria Teresa Dell’Anno: Stem Cells and Neurogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy
Elena Dvoretskova: Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy
Dejan Lazarevic: CBM Srl. Area Science park, Basovizza, SS14, km165, 34149 Trieste, Italy
Stefano Taverna: Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy
Damiana Leo: Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy
Tatyana D. Sotnikova: Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy
Andrea Menegon: Advanced Light and Electron Microscopy Bio-Imaging Centre, Experimental Imaging Centre, San Raffaele Scientific Institute, 20132 Milan, Italy
Paola Roncaglia: Sector of Neurobiology, International School for Advanced Studies (SISSA), via Bonomea, 265, 34136 Trieste, Italy
Giorgia Colciago: Stem Cells and Neurogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy
Giovanni Russo: Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy
Piero Carninci: Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-chô, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Gianni Pezzoli: Parkinson Institute, Istituti Clinici di Perfezionamento, 20126 Milan, Italy
Raul R. Gainetdinov: Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy
Stefano Gustincich: Sector of Neurobiology, International School for Advanced Studies (SISSA), via Bonomea, 265, 34136 Trieste, Italy
Alexander Dityatev: Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genoa, Italy
Vania Broccoli: Stem Cells and Neurogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy

Nature, 2011, vol. 476, issue 7359, 224-227

Abstract: Neurons from fibroblasts Three papers in this issue demonstrate the production of functional induced neuronal (iN) cells from human fibroblasts, a procedure that holds great promise for regenerative medicine. Pang et al. show that a combination of the three transcription factors Ascl1 (also known as Mash1), Brn2 (or Pou3f2) and Myt1l greatly enhances the neuronal differentiation of human embryonic stem cells. When combined with the basic helix–loop–helix transcription factor NeuroD1, these factors can also convert fetal and postnatal human fibroblasts into iN cells. Caiazzo et al. use a cocktail of three transcription factors to convert prenatal and adult mouse and human fibroblasts into functional dopaminergic neurons. The three are Mash1, Nurr1 (or Nr4a2) and Lmx1a. Conversion is direct with no reversion to a progenitor cell stage, and it occurs in cells from Parkinson's disease patients as well as from healthy donors. Yoo et al. use an alternative approach. They show that microRNAs can have an instructive role in neural fate determination. Expression of miR-9/9* and miR-124 in human fibroblasts induces their conversion into functional neurons, and the process is facilitated by the addition of some neurogenic transcription factors.

Date: 2011
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DOI: 10.1038/nature10284

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