Diverse reprogramming codes for neuronal identity

Rachel Tsunemoto, Sohyon Lee, Attila Szűcs, Pavel Chubukov, Irina Sokolova, Joel W. Blanchard, Kevin T. Eade, Jacob Bruggemann, Chunlei Wu, Ali Torkamani, Pietro Paolo Sanna and Kristin K. Baldwin ()
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Rachel Tsunemoto: Dorris Neuroscience Center, The Scripps Research Institute
Sohyon Lee: Dorris Neuroscience Center, The Scripps Research Institute
Attila Szűcs: University of California San Diego
Pavel Chubukov: Dorris Neuroscience Center, The Scripps Research Institute
Irina Sokolova: The Scripps Research Institute
Joel W. Blanchard: Dorris Neuroscience Center, The Scripps Research Institute
Kevin T. Eade: Dorris Neuroscience Center, The Scripps Research Institute
Jacob Bruggemann: The Scripps Research Institute
Chunlei Wu: The Scripps Research Institute
Ali Torkamani: Scripps Health and The Scripps Research Institute
Pietro Paolo Sanna: The Scripps Research Institute
Kristin K. Baldwin: Dorris Neuroscience Center, The Scripps Research Institute

Nature, 2018, vol. 557, issue 7705, 375-380

Abstract: Abstract The transcriptional programs that establish neuronal identity evolved to produce the rich diversity of neuronal cell types that arise sequentially during development. Remarkably, transient expression of certain transcription factors can also endow non-neural cells with neuronal properties. The relationship between reprogramming factors and the transcriptional networks that produce neuronal identity and diversity remains largely unknown. Here, from a screen of 598 pairs of transcription factors, we identify 76 pairs of transcription factors that induce mouse fibroblasts to differentiate into cells with neuronal features. By comparing the transcriptomes of these induced neuronal cells (iN cells) with those of endogenous neurons, we define a ‘core’ cell-autonomous neuronal signature. The iN cells also exhibit diversity; each transcription factor pair produces iN cells with unique transcriptional patterns that can predict their pharmacological responses. By linking distinct transcription factor input ‘codes’ to defined transcriptional outputs, this study delineates cell-autonomous features of neuronal identity and diversity and expands the reprogramming toolbox to facilitate engineering of induced neurons with desired patterns of gene expression and related functional properties.

Date: 2018
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DOI: 10.1038/s41586-018-0103-5

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