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Status |
Public on Jan 19, 2024 |
Title |
The circadian clock time tunes axonal regeneration |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Peripheral nervous system injuries lead to long-term neurological disability due to limited axonal regenerative ability. Injury-dependent and more recently injury-independent physiological mechanisms have provided important molecular insight into regenerative mechanisms. However, whether common molecular denominators underpinning both injury-dependent and independent biological processes exist remains unclear. We initially performed a comparative analysis of recently generated transcriptomic datasets associated with the regenerative ability of sciatic dorsal root ganglia (DRG). Surprisingly, circadian rhythms were identified as a the most significantly enriched biological process associated with regenerative capability. We demonstrate that DRG neurons possess an endogenous circadian clock with a 24h oscillations of circadian genes and that their regenerative ability displays a diurnal oscillation in a mouse model of sciatic nerve injury. Consistently, transcriptomic analysis of DRG neurons showed a significant time-of-day dependent enrichment for processes associated with neuronal development and axonal growth, for regeneration and circadian associated genes, including the core clock genes Bmal1 and Clock. Indeed, DRG-specific ablation of the non-redundant clock gene Bmal1showed that it is required for regenerative gene expression, neuronal intrinsic circadian axonal regeneration and target reinnervation. Lastly, Lithium, a chrono-active compound, enhanced nerve regeneration, in wildtype but not in clock genes Bmal1 and Cry1/2-deficient mice. Together, these data demonstrate that daily rhythms and the circadian clock fine-tune the regenerative response of DRG neurons, and they advocate for the use of chrono-active strategies in time-day dependent modulation of nerve repair.
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Overall design |
L4-6 dorsal root ganglia were extracted 72hr after a sciatic nerve injury at either Zeitgeber (ZT)8 or ZT20 followed by neuronal cell enrichment that was processed for RNA-seq
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Web link |
https://doi.org/10.1016/j.cmet.2023.10.012
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Contributor(s) |
De Virgiliis F, Müller F, Danzi M, Palmisano I, Di Giovanni S |
Citation(s) |
37951214 |
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Submission date |
Jun 23, 2023 |
Last update date |
Jan 19, 2024 |
Contact name |
Franziska Müller |
E-mail(s) |
f.mueller17@imperial.ac.uk
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Organization name |
Imperial College London
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Department |
Brain Sciences
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Lab |
Simone Di Giovanni
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Street address |
Du Cane Road
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City |
London |
ZIP/Postal code |
W12 0NN |
Country |
United Kingdom |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (7)
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Relations |
BioProject |
PRJNA986904 |
Supplementary file |
Size |
Download |
File type/resource |
GSE235687_tpm_anno.csv.gz |
1.1 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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