Rájová Jana, Davidsson Marcus, Avallone Martino, Hartnor Morgan, Aldrin-Kirk Patrick, Cardoso Tiago, Nolbrant Sara, Mollbrink Annelie, Storm Petter, Heuer Andreas, Parmar Malin, Björklund Tomas
Molecular Neuromodulation, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.
Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.
Mol Ther Methods Clin Dev. 2023 May 4;29:381-394. doi: 10.1016/j.omtm.2023.04.008. eCollection 2023 Jun 8.
Cell therapy for Parkinson's disease has experienced substantial growth in the past decades with several ongoing clinical trials. Despite increasing refinement of differentiation protocols and standardization of the transplanted neural precursors, the transcriptomic analysis of cells in the transplant after its full maturation has not been thoroughly investigated. Here, we present spatial transcriptomics analysis of fully differentiated grafts in their host tissue. Unlike earlier transcriptomics analyses using single-cell technologies, we observe that cells derived from human embryonic stem cells (hESCs) in the grafts adopt mature dopaminergic signatures. We show that the presence of phenotypic dopaminergic genes, which were found to be differentially expressed in the transplants, is concentrated toward the edges of the grafts, in agreement with the immunohistochemical analyses. Deconvolution shows dopamine neurons being the dominating cell type in many features beneath the graft area. These findings further support the preferred environmental niche of TH-positive cells and confirm their dopaminergic phenotype through the presence of multiple dopaminergic markers.
在过去几十年中，帕金森病的细胞治疗取得了显著进展，有多项临床试验正在进行。尽管分化方案日益完善，移植的神经前体细胞也实现了标准化，但移植细胞完全成熟后的转录组学分析尚未得到充分研究。在此，我们展示了对宿主组织中完全分化移植物的空间转录组学分析。与早期使用单细胞技术的转录组学分析不同，我们观察到移植物中源自人类胚胎干细胞（hESC）的细胞呈现出成熟的多巴胺能特征。我们发现，在移植物中差异表达的表型多巴胺能基因集中在移植物边缘，这与免疫组织化学分析结果一致。反卷积分析表明，多巴胺神经元是移植物区域下方许多特征中的主要细胞类型。这些发现进一步支持了TH阳性细胞偏好的环境生态位，并通过多种多巴胺能标记物的存在证实了它们的多巴胺能表型。
