Integrin β1 activity controls colony morphology during human pluripotent stem cell state transitions.

Area of Science:

• Stem cell biology
• Cell adhesion
• Developmental biology

Background:

• Integrin β1-mediated adhesion plays distinct roles in early versus later mouse embryogenesis.
• Pluripotent stem cells (PSCs) exist in naive and primed states with differing adhesion requirements.

Purpose of the Study:

• To investigate the role of integrin β1 in regulating naive-like and primed human induced PSC (hiPSC) states.
• To understand how integrin β1 activity influences hiPSC pluripotency and cell behavior in vitro.

Main Methods:

• Inhibition of integrin β1 in primed hiPSCs.
• Analysis of colony morphology, actomyosin contraction, and ERK activity.
• Gene expression profiling and single-cell transcriptomics.
• Functional assays to assess pluripotency transitions.

Main Results:

• Integrin β1 is active in both naive and primed hiPSCs.
• Inhibition of integrin β1 in primed hiPSCs induced naive-like colony features.
• Reduced actomyosin contraction and ERK activity were observed upon integrin β1 inhibition.
• Integrin β1 inhibition altered gene expression towards a more naive-like state.
• Single-cell transcriptomics revealed integrin β1's role in regulating transitions exiting naive pluripotency.

Conclusions:

• Integrin β1 signaling is a key regulator of human pluripotent stem cell states.
• Targeting integrin β1 can modulate hiPSC properties, offering potential for fine-tuning their function in vitro.
• These findings highlight integrin-dependent mechanisms governing pluripotency and cell fate decisions.