PDF(Pubmed)
Abstract：
Preterm cerebral white matter injury (WMI), a major form of prenatal brain injury, may potentially be treated by oligodendrocyte (OL) precursor cell (OPC) transplantation. However, the defective differentiation of OPCs during WMI seriously hampers the clinical application of OPC transplantation. Thus, improving the ability of transplanted OPCs to differentiate is critical to OPC transplantation therapy for WMI. We established a hypoxia-ischemia-induced preterm WMI model in mice and screened the molecules affected by WMI using single-cell RNA sequencing. We revealed that endothelin (ET)-1 and endothelin receptor B (ETB) are a pair of signaling molecules responsible for the interaction between neurons and OPCs and that preterm WMI led to an increase in the number of ETB-positive OPCs and premyelinating OLs. Furthermore, the maturation of OLs was reduced by knocking out ETB but promoted by stimulating ET-1/ETB signaling. Our research reveals a new signaling module for neuron-OPC interaction and provides new insight for therapy targeting preterm WMI.
摘要：
早产儿脑白质损伤(WMI),产前脑损伤的主要形式，可以通过少突胶质细胞(OL)前体细胞(OPC)移植进行治疗。然而,WMI过程中OPCs的分化缺陷严重阻碍了OPC移植的临床应用。因此，提高移植OPCs的分化能力是OPCs移植治疗WMI的关键。我们在小鼠中建立了缺氧缺血诱导的早产WMI模型，并使用单细胞RNA测序筛选了受WMI影响的分子。我们发现内皮素（ET）-1和内皮素受体B（ETB）是一对负责神经元和OPCs之间相互作用的信号分子，早产WMI导致ETB阳性OPCs和髓鞘形成前OLs的数量增加。此外，通过敲除ETB减少了OLs的成熟，但通过刺激ET-1/ETB信号促进了OLs的成熟。我们的研究揭示了神经元-OPC相互作用的新信号传导模块，并为针对早产WMI的治疗提供了新的见解。
