Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions.

Area of Science:

• Stem Cell Biology
• Cell Adhesion Mechanisms
• Developmental Biology

Background:

• Human embryonic stem cells (hESCs) form colonies with strong intercellular adhesion.
• This architecture is crucial for hESC self-renewal, pluripotency, and survival.
• Key proteins involved include epithelial cadherin (E-cadherin), nonmuscle myosin IIA (NMMIIA), and p120-catenin.

Purpose of the Study:

• To elucidate the molecular mechanisms regulating intercellular adhesion and cellular architecture in hESCs.
• To understand the role of the E-cadherin/p120-catenin/NMMIIA network in hESC self-renewal and survival.
• To investigate the impact of this network on somatic cell reprogramming.

Main Methods:

• Analysis of the positive feedback loop between E-cadherin and p120-catenin.
• Investigation of NMMIIA's role in stabilizing p120-catenin and E-cadherin-mediated adhesion.
• Assessment of the effects of perturbing this signaling network on hESC colony formation, pluripotency, and survival.
• Evaluation of E-cadherin depletion's impact on somatic cell reprogramming efficiency.

Main Results:

• E-cadherin and p120-catenin form a positive feedback loop, enhancing E-cadherin accumulation at intercellular junctions.
• NMMIIA stabilizes p120-catenin and regulates E-cadherin-mediated adhesion.
• Disruption of this network leads to impaired colony formation, loss of pluripotency, and reduced hESC survival.
• Depletion of E-cadherin significantly reduces reprogramming efficiency of somatic cells to an ESC-like state.

Conclusions:

• The mechanical-biochemical integration within the E-cadherin/p120-catenin/NMMIIA network is critical for maintaining hESC identity and architecture.
• This network provides mechanistic insights into intercellular adhesion regulation during hESC self-renewal.
• Understanding these mechanisms is vital for advancing hESC applications and somatic reprogramming technologies.