Diverse reprogramming codes for neuronal identity

Rachel Tsunemoto, Sohyon Lee, A. Szűcs, Pavel Chubukov, Irina Sokolova, Joel W. Blanchard, Kevin T. Eade, Jacob Bruggemann, Chunlei Wu, Ali Torkamani, Pietro Paolo Sanna, Kristin K. Baldwin

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)375-380
Number of pages6
JournalNature
Volume557
Issue number7705
DOIs
Publication statusPublished - May 17 2018

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Transcription Factors
Neurons
Gene Regulatory Networks
Transcriptome
Fibroblasts
Pharmacology
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Tsunemoto, R., Lee, S., Szűcs, A., Chubukov, P., Sokolova, I., Blanchard, J. W., ... Baldwin, K. K. (2018). Diverse reprogramming codes for neuronal identity. Nature, 557(7705), 375-380. https://doi.org/10.1038/s41586-018-0103-5

Diverse reprogramming codes for neuronal identity. / Tsunemoto, Rachel; Lee, Sohyon; Szűcs, A.; Chubukov, Pavel; Sokolova, Irina; Blanchard, Joel W.; Eade, Kevin T.; Bruggemann, Jacob; Wu, Chunlei; Torkamani, Ali; Sanna, Pietro Paolo; Baldwin, Kristin K.

In: Nature, Vol. 557, No. 7705, 17.05.2018, p. 375-380.

Research output: Contribution to journalArticle

Tsunemoto, R, Lee, S, Szűcs, A, Chubukov, P, Sokolova, I, Blanchard, JW, Eade, KT, Bruggemann, J, Wu, C, Torkamani, A, Sanna, PP & Baldwin, KK 2018, 'Diverse reprogramming codes for neuronal identity', Nature, vol. 557, no. 7705, pp. 375-380. https://doi.org/10.1038/s41586-018-0103-5
Tsunemoto R, Lee S, Szűcs A, Chubukov P, Sokolova I, Blanchard JW et al. Diverse reprogramming codes for neuronal identity. Nature. 2018 May 17;557(7705):375-380. https://doi.org/10.1038/s41586-018-0103-5
Tsunemoto, Rachel ; Lee, Sohyon ; Szűcs, A. ; Chubukov, Pavel ; Sokolova, Irina ; Blanchard, Joel W. ; Eade, Kevin T. ; Bruggemann, Jacob ; Wu, Chunlei ; Torkamani, Ali ; Sanna, Pietro Paolo ; Baldwin, Kristin K. / Diverse reprogramming codes for neuronal identity. In: Nature. 2018 ; Vol. 557, No. 7705. pp. 375-380.
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