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Publication : Transcriptional dynamics of murine motor neuron maturation in vivo and in vitro.

First Author  Patel T Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  5427
PubMed ID  36109497 Mgi Jnum  J:328990
Mgi Id  MGI:7340828 Doi  10.1038/s41467-022-33022-4
Citation  Patel T, et al. (2022) Transcriptional dynamics of murine motor neuron maturation in vivo and in vitro. Nat Commun 13(1):5427
abstractText  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.
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