RESULTS: We assessed the impact of maternal SARS-CoV-2 on HBCs isolated from 24 term placentas (N = 10 SARS-CoV-2 positive cases, 14 negative controls). Using single-cell RNA-sequencing, we demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells (HBC-iMGs), with impaired synaptic pruning behavior compared to HBC models from negative controls.
CONCLUSIONS: These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.
结果:我们评估了母亲SARS-CoV-2对从24个足月胎盘中分离出的HBCs的影响(N=10例SARS-CoV-2阳性病例,14个阴性对照)。使用单细胞RNA测序,我们证明了HBC亚群表现出不同的细胞程序,特定的亚群受到SARS-CoV-2的差异影响。对差异表达基因的评估暗示吞噬作用受损,HBCs和小胶质细胞的关键功能,在一些子集群中。利用先前验证的小胶质细胞突触修剪模型,我们表明,从SARS-CoV-2阳性妊娠胎盘中分离出的HBCs可以转分化为小胶质细胞样细胞(HBC-iMGs),与阴性对照的HBC模型相比,突触修剪行为受损。
结论:这些发现表明,出生时分离的HBC可用于创建后代小胶质细胞编程的个性化细胞模型。