在发表于Genome Biology上的Mapping human pluripotent stem cell differentiation pathways using high throughput single-cell RNA-sequencing文章中,来自浙江大学的Haide Chen、Guoji Guo及其研究团队使用高通量单细胞RNA测序法(scRNA-seq),在优化的微流体环路基础上分析了人胚胎体系中的早期分化谱系。
Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved.
Results
We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells. Through pseudotime analysis, we construct the developmental trajectories of these progenitor cells and reveal the gene expression dynamics in the process of cell differentiation. We further reprogram primed H9 cells into naïve-like H9 cells to study the cellular-state transition process. We find that genes related to hemogenic endothelium development are enriched in naïve-like H9. Functionally, naïve-like H9 show higher potency for differentiation into hematopoietic lineages than primed cells.
Conclusions
Our single-cell analysis reveals the cellular-state landscape of hPSC early differentiation, offering new insights that can be harnessed for optimization of differentiation protocols.
Genome Biology (https://genomebiology.biomedcentral.com/, 13.2 - 2-year Impact Factor, 16.5 - 5-year Impact Factor) publishes outstanding research in all areas of biology and biomedicine studied from a genomic and post-genomic perspective.
The current impact factor is 13.214* and the journal is ranked 4th among research journals in the Genetics and Heredity category by Thomson Reuters. Genome Biology is the highest ranked open access journal in the category.