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Mapping human pluripotent stem cell differentiation pathways using high throughput single-cell RNA-sequencing

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. | Han et al. Genome Biology 2018 19 47 https doi.org 10.1186 s13059-018-1426-0 RESEARCH Open Access Mapping human pluripotent stem cell differentiation pathways using high throughput single-cell RNA-sequencing Xiaoping Han1 2 8 Haide Chen1 3 5 Daosheng Huang1 8 Huidong Chen4 6 Lijiang Fei1 8 Chen Cheng7 He Huang2 8 Guo-Cheng Yuan4 and Guoji Guo1 2 3 8 Abstract Background 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. Keywords Single-cell RNA-sequencing Primed human pluripotent stem cell Embryoid body Naïve human pluripotent stem cell Background existing protocols suffer from low efficiency and functional Thomson et al. derived human pluripotent stem cells deficiency. hPSCs from human blastocysts for the first time in 1998 In