MicroRNA Let-7 Promotes Migration Of Oligodendrocyte Precursor Cells In Preterm White Matter Injury In Vitro

Preterm white matter injury(PWMI)is a major type of brain injuries in preterm postnatal complications.Children with PWMI often develop cerebral palsy and cognitive defects later in life.In preterm infants,the migration and development of oligodendrocyte precursor cells(OPCs)are severely disturbed due to repeated ischemia,hypoxia and inflammatory responses,causing disorders in myelin formation and eventually leading to white matter damage.Obstructed migration of OPCs is one of the main causes of many known demyelinating diseases.It is important to identify the molecular mechanisms underlying the process of white matter damage in preterm infants.Micro RNAs are endogenous non-coding small RNAs with a length of about 18-25 nucleotides.They are highly conserved in evolution and highly specific in tissues,and play key roles in posttranscriptional regulation,thus regulating multiple cellular functions,including cell migration and metabolisms.The development of OPCs is a highly coordinated process,and is directed by a variety of internal and external factors,such as growth factors,neural transmitters and epigenetic regulations.However,the molecular mechanism of OPCs migration is still not fully understood.In this study,we optimized the in vitro culturing procedure of OPCs from mouse model of PWMI,and performed micro RNA sequencing and RT-PCR.We found that micro RNA let-7 family decreased in PWMI samples.Overexpressing of let-7 promoted the migration of OPCs in vitro.RNA sequencing data suggest that Itgav,Nrg1,Nexn and Sulf1 may be potential target genes of let-7 in PWMI.In addition,single-cell sequencing of human-derived oligodendrocyte progenitor cells showed that human-derived OPCs were of high homogenous population of cells,suggesting these cells may have potential value in clinical applications for the treatment of demyelination disorders.