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Sexual dimorphism of early transcriptional reprogramming in degenerating peripheral nerves

ABSTRACT: Transcriptional changes are distinct in female and male mice in the time course of peripheral nerve injury response. Here, we present sexually dimorphic transcriptome profiles established in the space of 24 h period after sciatic nerve axotomy.

ORGANISM(S): Mus musculus

PROVIDER: GSE182751 | GEO | 2022/10/11

REPOSITORIES: GEO

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Proximal sciatic nerve stumps exhibit sexually dimorphic transcriptome changes in mice after peripheral nerve injury (axotomy)

Project description:Transcriptional changes are distinct in female and male mice in the time course of peripheral nerve injury response. Here, we present sexually dimorphic transcriptome profiles established in the space of 24 h period after sciatic nerve axotomy.

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Sexual dimorphism of early transcriptional reprogramming in dorsal root ganglia after peripheral nerve injury

Project description:Peripheral nerve injury induces genome-wide transcriptional reprogramming of first-order neurons and auxiliary cells of dorsal root ganglia (DRG). Accumulating experimental evidence suggests that onset and mechanistic principles of post-nerve injury processes are sexually dimorphic. We examined largely understudied aspects of early transcriptional events in DRG within 24 h after sciatic nerve axotomy in mice of both sexes. Using high-depth RNA sequencing (>50 million reads/sample) to pinpoint sexually dimorphic changes related to regeneration, immune response, bioenergy, and sensory functions, we identified a higher number of transcriptional changes in male relative to female DRG. In males, the induction of innate immune cascades via TLR, chemokine, and Csf1-receptor axis, robust regenerative programs driven by Sox, Twist1/2, Pax5/9 transcription factors were accompanied by a decline in ion channel transcripts. Females demonstrated nerve injury-specific transcriptional co-activation of the actinin 2 networks. The predicted upstream regulators and interactive networks highlighted the role of novel epigenetic factors and genetic linkage to sex chromosomes as hallmarks of gene regulation post-PNI. We implicated epigenetic X chromosome inactivation in the regulation of immune response activity uniquely in females. Sexually dimorphic regulation of MMP/ADAMTS metalloproteinases and their intrinsic X-linked regulator Timp1 contributes to extracellular matrix remodeling integrated with pro-regenerative and immune functions. Lexis1 noncoding RNA involved in LXR-mediated lipid metabolism was identified as a novel nerve injury marker. Together, our data identified unique early response triggers of sex-specific peripheral nerve injury regulation to gain mechanistic insights into the origin of female- and male-prevalent sensory neuropathies.

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Sham operated mouse sciatic nerve for studies of sexual dimorphism of peripheral nerve injury (PNI)

Project description:Accumulating evidence suggests that transcriptional changes are distinct in females and males in the time course of peripheral nerve injury response. Here, we present sexually dimorphic transcriptome profiles established within 24 h period after sham operation.

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Sexual dimorphism of early transcriptional reprogramming in degenerating peripheral nerves.

Project description: Not available

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Proximal sciatic nerve stumps exhibit sexually dimorphic transcriptome changes in mice after peripheral nerve injury (axotomy)

Project description:Proximal sciatic nerve stumps exhibit sexually dimorphic transcriptome changes in mice after peripheral nerve injury (axotomy)

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Hepatic BCL6 and plasma triglycerides regulate sexual dimorphism in tissue tolerance [set 5]

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Sexual dimorphism in transcriptomic response to fluocinolone acetonide (FA) in murine epidermis

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MicroRNA profiling in dorsal root ganglion after sciatic nerve injury

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