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Single cell multi-omics analysis reveals novel roles for DNA methylation in sensory neuron injury responses

ABSTRACT: Single cell multi-omics analysis reveals novel roles for DNA methylation in sensory neuron injury responses

PROVIDER: PRJNA513289 | ENA |

REPOSITORIES: ENA

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Single cell multi-omics analysis reveals novel roles for DNA methylation in sensory neuron injury responses

Project description:We used single cell multi-omics method to simultaneously profiled both DNA methylome and mRNA transcriptome from single DRG sensory neurons under either control or peripheral nerve injury condition.

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Transcriptional reprogramming of distinct peripheral sensory neuron subtypes after axonal injury

Project description:Primary somatosensory neurons specialize in transmitting distinct types of sensory information through differences in cell size, myelination, and the expression of various receptors and ion channels, which together define their transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we find that the different somatosensory neuronal subtypes undergo a similar transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming, which is not observed in non-neuronal cells from sensory ganglia, resolves over a similar time course as target reinnervation and is associated with the restoration of original cell identity. Injury-induced transcriptional reprogramming requires ATF3, a transcription factor which is induced rapidly after injury and necessary for axonal regeneration and functional recovery. Our findings suggest that the transcription factors induced early after peripheral sensory neuron injury promote their transcriptional and functional metamorphosis, analogous to their known roles in reprogramming cell fate.

2020-07-22 | GSE154659 | GEO

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Transcriptional reprogramming of distinct peripheral sensory neuron subtypes after axonal injury

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Transcriptome analysis of metronidazole-induced sensory neuron ablation in zebrafish

Project description:Damage to and/or loss of sensory neurons can result in debilitating neuropathies that often have a dramatic impact on quality of life. The cellular mechanisms involved in the response of neurons and glia to such pathological insults are poorly understood. Investigation has shown that peripheral glia play critical roles in both the degenerative and regenerative processes that are involved in the responses to peripheral nerve damage. The vast majority of studies have focused primarily on myelinating Schwann cells], with the result that very little is known regarding how the non-myelinating glia that ensheath axons and neuronal somas respond to nerve damage. This is a significant knowledge gap, given that over 80% of cutaneous fibers are unmyelinated, that they transduce such important modalities as itch, pain, temperature, touch and pressure, and that they are affected in many prevalent peripheral neuropathies. It is the goal of this study to shed light on the genetic programs involved in the responses of non-myelinating glia roles to nerve degeneration. We utilized RNA-seq to identify genes that were differentially expressed in the larval head during the process of sensory neuron ablation and axon degeneration in both wild-type larvae and in larvae that do not have peripheral glia (foxd3 mutants) using a selective, conditional approach. Overall, the information regarding differential gene expression in these conditions will provide a basis for further investigation into the cellular processes that underlie pathophysiological responses of neurons and glia to sensory nerve damage.

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Evaluation of Tmem184b dependent gene expression changes during sensory neuron differentiation in vitro

Project description:Our objective was to evaluate the gene expression changes occuring in early sensory neuron development that were lost in the absence of Tmem184b and restored upon its reintroduction into mutant neurons in culture.

2020-07-15 | GSE154435 | GEO

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