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

Tulsi Patel (), Jennifer Hammelman, Siaresh Aziz, Sumin Jang, Michael Closser, Theodore L. Michaels, Jacob A. Blum, David K. Gifford and Hynek Wichterle ()
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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

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33022-4

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