Ludwig Institute for Cancer Research, Box 240, SE-171 77, Stockholm, Sweden.
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Nat Commun. 2020 May 15;11(1):2434. doi: 10.1038/s41467-020-16225-5.
Cell replacement is a long-standing and realistic goal for the treatment of Parkinson's disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.
细胞替代疗法是治疗帕金森病 (PD) 的一个长期而现实的目标。可用于移植的细胞可以从胎儿脑组织或干细胞中获得。然而，移植后，多巴胺 (DA) 神经元被视为移植物的一个次要组成部分，而且一直难以确定其他细胞类型的身份。在这里，我们报告了单细胞 RNA 测序 (scRNA-seq) 与全面组织学分析相结合的分析结果，以描述在临床前大鼠 PD 模型中功能成熟后的人类胚胎干细胞 (hESC) 和胎儿组织的脑内移植物。我们表明，神经元和星形胶质细胞是胎儿和干细胞来源移植物的主要组成部分。此外，我们还鉴定出一种与干细胞来源移植物中最近鉴定的一类血管周样细胞非常相似的细胞类型。因此，这项研究揭示了在临床相关细胞替代 PD 模型中以前未知的细胞多样性。
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