Cellular population dynamics shape the route to human pluripotency

Area of Science:

• Cellular biology
• Stem cell research
• Biotechnology

Background:

• Human cellular reprogramming to induced pluripotency remains inefficient, limiting the study of intermediate stages.
• Understanding extrinsic factors influencing reprogramming is crucial for improving efficiency.

Purpose of the Study:

• To identify and resolve distinct subpopulations and their interactions during high-efficiency reprogramming.
• To elucidate the role of extracellular context and cell population determinants in human cellular reprogramming.

Main Methods:

• Utilized microfluidics for high-efficiency reprogramming.
• Performed temporal multi-omics, including secretome analysis and single-cell transcriptomics.
• Investigated protein communication pathways and extracellular environment remodeling.

Main Results:

• Identified functional extrinsic pathways of protein communication between reprogramming subpopulations.
• Demonstrated the HGF/MET/STAT3 axis as a potent enhancer of reprogramming.
• Showcased HGF accumulation in microfluidics enhances reprogramming, while exogenous supply is needed in conventional dishes.

Conclusions:

• Human cellular reprogramming is transcription factor-driven but heavily relies on extracellular context.
• Cell population determinants and extrinsic signaling pathways significantly impact reprogramming efficiency.
• Microfluidic systems can optimize reprogramming by facilitating endogenous factor accumulation.