基于单细胞测序技术对hUC-MSCs移植新生大鼠脑白质损伤后pre-OL转化与机制的研究

脑室周围白质软化（PVL）是早产儿脑损伤最常见的表现形式之一，可造成神经系统后遗症，如何改善脑损伤早产儿的长期预后是亟待解决的临床问题。早产儿脑损伤的靶细胞主要为少突胶质细胞(OL)和其前体细胞(pre-OL)。项目组前期研究发现将人脐带间充质干细胞(hUC-MSCs)用于新生大鼠PVL脑损伤模型脑室内移植后，其可参与神经损伤修复。本项目拟采用孕期LPS法构建新生大鼠PVL模型，采用hUC-MSCs脑室内定向移植，观察其对脑白质损伤后OL和pre-OL细胞修复能力的影响，并以单细胞转录组测序技术确定PVL发生过程中及hUC-MSCs移植后脑组织中异质细胞群体的细胞类型和细胞状态，确定脑白质损伤过程和损伤后修复中特征性差异表达的基因，寻找影响脑白质损伤发生发展以及移植改善脑白质损伤表型的新机制，为临床应用hUC-MSCs移植治疗早产儿脑白质损伤提供理论依据，为疾病的精准医疗探索新方向。

Periventricular leukomalacia (PVL) is one of the most common manifestations of brain injury in preterm infants, which can cause neurological sequelae, such as cerebral palsy, cognitive impairment, audio-visual dysfunction, epilepsy, etc., resulting in poor quality of life in preterm infants. How to improve the long-term prognosis of premature infants with brain injury is an urgent clinical problem. Oligodendrocytes (OL) and their precursor cells (pre-OL) are the main target cells of brain injury in preterm infants. The results of previous studies in the project group suggested that human umbilical cord mesenchymal stem cells (hUC-MSCs) could participate in the repair of nerve injury after intraventricular transplantation of PVL brain injury model in newborn rats. The purpose of this study is to establish a PVL newborn rat model by LPS during pregnancy, and to observe the effect of hUC-MSCs on the repair ability of OL and pre-OL cells in rats with brain white matter injury by intraventricular directional transplantation, and to determine the cell types and cell states of heterogeneous cell groups in brain tissue during PVL and after hUC-MSCs transplantation, and to explore the neutralization and damage of brain white matter injury. This study is aimed to provide theoretical basis for clinical transplantation of hUC-MSCs in the treatment of premature infant's brain white matter injury, and to explore a new direction for the precise medical treatment of the disease.