Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons

The expression of linear DNA sequence is precisely regulated by the three-dimensional(3D)architecture of chromatin.Morphine-induced aberrant gene networks of neurons have been extensively investigated;however,how morphine impacts the 3D genomic architecture of neurons is still unknown.Here,we applied digestion-ligation-only high-throughput chromosome conformation capture(DLO Hi-C)technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons.After receiving continuous morphine administration for 90 days on rhesus monkeys,we discovered that morphine re-arranged chromosome territories,with a total of 391 segmented compartments being switched.Morphine altered over half of the detected topologically associated domains(TADs),most of which exhibited a variety of shifts,followed by separating and fusing types.Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops.Moreover,all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops,and were further validated for changed expression.Collectively,an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects.Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.

Three-dimensional-printed collagen/chitosan/secretome derived from HUCMSCs scaffolds for efficient neural network reconstruction in canines with traumatic brain injury

The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury(TBI).We aimed to determine the effect of 3D-printed collagen/chitosan/secretome derived from human umbilical cord blood mesenchymal stem cells scaffolds(3D-CC-ST)on the injured tissue regeneration process.3D-CC-ST was performed using 3D printing technology at a low temperature(20C),and the physical properties and degeneration rate were measured.The utilization of low temperature contributed to a higher cytocompatibility of fabricating porous 3D architectures that provide a homogeneous distribution of cells.Immediately after the establishment of the canine TBI model,3D-CC-ST and 3D-CC(3D-printed collagen/chitosan scaffolds)were implanted into the cavity of TBI.Following implantation of scaffolds,neurological examination and motor evoked potential detection were performed to analyze locomotor function recovery.Histological and immunofluorescence staining were performed to evaluate neuro-regeneration.The group treated with 3D-CC-ST had good performance of behavior functions.Implanting 3D-CC-ST significantly reduced the cavity area,facilitated the regeneration of nerve fibers and vessel reconstruction,and promoted endogenous neuronal differentiation and synapse formation after TBI.The implantation of 3D-CC-ST also markedly reduced cell apoptosis and regulated the level of systemic inflammatory factors after TBI.