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Transcriptional dynamics of murine motor neuron maturation in vivo and in vitro

Author

Listed:
  • Tulsi Patel

    (Columbia University Irving Medical Center)

  • Jennifer Hammelman

    (MIT)

  • Siaresh Aziz

    (Columbia University Irving Medical Center)

  • Sumin Jang

    (Columbia University Irving Medical Center)

  • Michael Closser

    (Columbia University Irving Medical Center)

  • Theodore L. Michaels

    (Columbia University Irving Medical Center)

  • Jacob A. Blum

    (Stanford University School of Medicine)

  • David K. Gifford

    (MIT)

  • Hynek Wichterle

    (Columbia University Irving Medical Center)

Abstract

Neurons born in the embryo can undergo a protracted period of maturation lasting well into postnatal life. How gene expression changes are regulated during maturation and whether they can be recapitulated in cultured neurons remains poorly understood. Here, we show that mouse motor neurons exhibit pervasive changes in gene expression and accessibility of associated regulatory regions from embryonic till juvenile age. While motifs of selector transcription factors, ISL1 and LHX3, are enriched in nascent regulatory regions, motifs of NFI factors, activity-dependent factors, and hormone receptors become more prominent in maturation-dependent enhancers. Notably, stem cell-derived motor neurons recapitulate ~40% of the maturation expression program in vitro, with neural activity playing only a modest role as a late-stage modulator. Thus, the genetic maturation program consists of a core hardwired subprogram that is correctly executed in vitro and an extrinsically-controlled subprogram that is dependent on the in vivo context of the maturing organism.

Suggested Citation

  • Tulsi Patel & Jennifer Hammelman & Siaresh Aziz & Sumin Jang & Michael Closser & Theodore L. Michaels & Jacob A. Blum & David K. Gifford & Hynek Wichterle, 2022. "Transcriptional dynamics of murine motor neuron maturation in vivo and in vitro," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33022-4
    DOI: 10.1038/s41467-022-33022-4
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    1. Roman A. Romanov & Evgenii O. Tretiakov & Maria Eleni Kastriti & Maja Zupancic & Martin Häring & Solomiia Korchynska & Konstantin Popadin & Marco Benevento & Patrick Rebernik & Francois Lallemend & Ka, 2020. "Molecular design of hypothalamus development," Nature, Nature, vol. 582(7811), pages 246-252, June.
    2. Feng Yue & Yong Cheng & Alessandra Breschi & Jeff Vierstra & Weisheng Wu & Tyrone Ryba & Richard Sandstrom & Zhihai Ma & Carrie Davis & Benjamin D. Pope & Yin Shen & Dmitri D. Pervouchine & Sarah Djeb, 2014. "A comparative encyclopedia of DNA elements in the mouse genome," Nature, Nature, vol. 515(7527), pages 355-364, November.
    3. Kathryn C. Allaway & Mariano I. Gabitto & Orly Wapinski & Giuseppe Saldi & Chen-Yu Wang & Rachel C. Bandler & Sherry Jingjing Wu & Richard Bonneau & Gord Fishell, 2021. "Genetic and epigenetic coordination of cortical interneuron development," Nature, Nature, vol. 597(7878), pages 693-697, September.
    4. Jon E. Chatterton & Marc Awobuluyi & Louis S. Premkumar & Hiroto Takahashi & Maria Talantova & Yeonsook Shin & Jiankun Cui & Shichun Tu & Kevin A. Sevarino & Nobuki Nakanishi & Gang Tong & Stuart A. L, 2002. "Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits," Nature, Nature, vol. 415(6873), pages 793-798, February.
    5. Caryn S. Ross-Innes & Rory Stark & Andrew E. Teschendorff & Kelly A. Holmes & H. Raza Ali & Mark J. Dunning & Gordon D. Brown & Ondrej Gojis & Ian O. Ellis & Andrew R. Green & Simak Ali & Suet-Feung C, 2012. "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer," Nature, Nature, vol. 481(7381), pages 389-393, January.
    6. HaoSheng Sun & Oliver Hobert, 2021. "Temporal transitions in the post-mitotic nervous system of Caenorhabditis elegans," Nature, Nature, vol. 600(7887), pages 93-99, December.
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    Cited by:

    1. Ee Shan Liau & Suoqin Jin & Yen-Chung Chen & Wei-Szu Liu & Maëliss Calon & Stéphane Nedelec & Qing Nie & Jun-An Chen, 2023. "Single-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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