Revealing induced pluripotent stem cells' potential as a better alternative to embryonic stem cells for Parkinson's disease treatment based on single-cell RNA-seq

Braz J Med Biol Res. 2024 Dec 13:57:e13482. doi: 10.1590/1414-431X2024e13482. eCollection 2024.

Abstract

Both embryonic stem cells (ESCs) and the successful reprogramming of induced pluripotent stem cells (iPSCs) offer an unprecedented therapeutic potential for Parkinson's disease (PD), allowing for the replacement of depleted neurons in PD-affected brain regions, thereby achieving therapeutic goals. This study explored the differences in cell types between iPSCs and ESCs in the PD brain to provide a feasible theoretical basis for the improved use of iPSCs as a replacement for ESCs in treating PD. Signal cell RNA sequencing data and microarray data of ESCs and iPSCs were collected from the GEO database. scRNA-seq data were subjected to quality control, clustering, and identification using the Seurat R package to determine cell types and proportions in ESCs and iPSCs. Differential expression analysis was performed to identify differentially expressed genes between ESCs and iPSCs, and PPI network analysis was conducted using String. Based on scRNA-seq data, we identified 13 cell clusters in ESCs and 13 cell clusters in iPSCs. iPSCs were predominantly composed of immune cells and lacked astrocytes, neurons, and dopamine neurons compared to ESCs. iPSCs also exhibited lower cell type diversity compared to ESCs. At the gene level, iPSCs lacked key genes, such as TH and GAP43 for nerve growth and development. At the metabolic level, the difference between ESCs and iPSC was mainly reflected in nerve cells and was closely related to the tumor-proliferation signature. iPSCs can be promoted to differentiate into cell types closer to or even replace ESCs, providing a better therapeutic option for PD treatment.

MeSH terms

  • Cell Differentiation
  • Embryonic Stem Cells*
  • Humans
  • Induced Pluripotent Stem Cells*
  • Parkinson Disease* / genetics
  • Parkinson Disease* / therapy
  • RNA-Seq
  • Single-Cell Analysis / methods
  • Single-Cell Gene Expression Analysis

Grants and funding

This work was supported by grants from the Central Government Guides Local Science and Technology Development Funds (YDZX2022091), the Taishan Scholars Program of Shandong Province (tsqn201909148), and Shandong Sport University Introduction of Talent Research Start-up Fund (No. 2021009).