TY - JOUR
T1 - Mapping human pluripotent stem cell differentiation pathways using high throughput single-cell RNA-sequencing
AU - Han, Xiaoping
AU - Chen, Haide
AU - Huang, Daosheng
AU - Chen, Huidong
AU - Fei, Lijiang
AU - Cheng, Chen
AU - Huang, He
AU - Yuan, Guo Cheng
AU - Guo, Guoji
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/4/5
Y1 - 2018/4/5
N2 - 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.
AB - 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.
KW - Embryoid body
KW - Naïve human pluripotent stem cell
KW - Primed human pluripotent stem cell
KW - Single-cell RNA-sequencing
UR - http://www.scopus.com/inward/record.url?scp=85044993376&partnerID=8YFLogxK
U2 - 10.1186/s13059-018-1426-0
DO - 10.1186/s13059-018-1426-0
M3 - Article
C2 - 29622030
AN - SCOPUS:85044993376
SN - 1474-7596
VL - 19
JO - Genome Biology
JF - Genome Biology
IS - 1
M1 - 47
ER -