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Series GSE235687 Query DataSets for GSE235687
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
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.
 
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
Web link https://doi.org/10.1016/j.cmet.2023.10.012
 
Contributor(s) De Virgiliis F, Müller F, Danzi M, Palmisano I, Di Giovanni S
Citation(s) 37951214
Submission date Jun 23, 2023
Last update date Jan 19, 2024
Contact name Franziska Müller
E-mail(s) f.mueller17@imperial.ac.uk
Organization name Imperial College London
Department Brain Sciences
Lab Simone Di Giovanni
Street address Du Cane Road
City London
ZIP/Postal code W12 0NN
Country United Kingdom
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (7)
GSM7507905 ZT20, rep1
GSM7507906 ZT20, rep2
GSM7507907 ZT20, rep3
Relations
BioProject PRJNA986904

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Supplementary file Size Download File type/resource
GSE235687_tpm_anno.csv.gz 1.1 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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