EZH2-dependent myelination following sciatic nerve injury

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

Developmental Temporal Patterns and Molecular Network Features in the Transcriptome of Rat Spinal Cord

The molecular network features of spinal cord development that are integral to tissue engineering remain poorly understood in placental mammals,especially in terms of their relationships with vital biological processes such as regeneration.Here,using a large-scale temporal transcriptomic analysis of rat spinal cord from the embryonic stage to adulthood,we show that fluctuating RNA expression levels reflect highly active transcriptional regulation,which may initiate spinal cord patterning.We also demonstrate that microRNAs(miRNAs)and transcriptional factors exhibit a mosaic profile based on their expression patterns,while differential alternative splicing events reveal that alternative splicing may be a driving force for the development of the node of Ranvier.Our study also supports the existence of a negative correlation between innate immunity and intrinsic growth capacity.Epigenetic modifications appear to perform their respective regulatory functions at different stages of development,while guanine nucleotidebinding protein(G protein)-coupled receptors(including olfactory receptors(ORs))may perform pleiotropic roles in axonal growth.This study provides a valuable resource for investigating spinal cord development and complements the increasing number of single-cell datasets.These findings also provide a genetic basis for the development of novel tissue engineering strategies.

Skin derived precursors induced Schwann cells mediated tissue engineering-aided neuroregeneration across sciatic nerve defect

A central question in neural tissue engineering is how the tissue-engineered nerve(TEN)translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes.Here,we report a skin-derived precursor-induced Schwann cell(SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft(SKP-SCs-TEN)that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral,histological,and electrophysiological evidence.For achieving better effect of neuroregeneration,this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix(ECM).To overcome the limitation of traditional tissue-engineered nerve grafts,jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration.To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration,we performed a cDNA microarray analysis of gene expression profiling,a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues.A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration.Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.