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Nature. 2018 May;557(7705):375-380. doi: 10.1038/s41586-018-0103-5. Epub 2018 May 9.

Diverse reprogramming codes for neuronal identity.

Author information

1
Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.
2
Neuroscience Graduate Program, University of California San Diego, La Jolla, CA, USA.
3
BioCircuits Institute, University of California San Diego, La Jolla, CA, USA.
4
MTA-ELTE-NAP B Neuronal Cell Biology Research Group, Eotvos Lorand University, Budapest, Hungary.
5
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA, USA.
6
Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
7
Scripps Translational Science Institute, Scripps Health and The Scripps Research Institute, La Jolla, CA, USA.
8
Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA. kbaldwin@scripps.edu.
9
Neuroscience Graduate Program, University of California San Diego, La Jolla, CA, USA. kbaldwin@scripps.edu.

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.

PMID:
29743677
PMCID:
PMC6483730
DOI:
10.1038/s41586-018-0103-5
[Indexed for MEDLINE]
Free PMC Article

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