Authors: Tianshu Feng Eva Szabo Ewa Dziak Michal Opas
Publish Date: 2010/02/11
Volume: 6, Issue: 1, Pages: 74-85
Abstract
Biomechanical signals such as cell shape and spreading play an important role in controlling stem cell commitment Cell shape adhesion and spreading are also affected by calreticulin a multifunctional calciumbinding protein which influences several cellular processes including adipogenesis Here we show that cytoskeletal disruption in mouse embryonic stem cells using cytochalasin D or nocodazole promotes adipogenesis While cytochalasin D disrupts stress fibres and inhibits focal adhesion formation nocodazole depolymerises microtubules and promotes focal adhesion formation Furthermore cytochalasin D increases the levels of both total and activated calcium/calmodulindependent protein kinase II whereas nocodazole decreases it Nevertheless both treatments significantly increase the adipogenic potential of embryonic stem cells in vitro Both cytochalasin D and nocodazole exposure caused cell rounding suggesting that it is cell shape that causes the switch towards the adipogenic programme Calreticulincontaining embryonic stem cells under baseline conditions show low adipogenic potential have low activity of signalling via calcium/calmodulindependent protein kinase II and display normal adhesive properties and cellular spreading in comparison to the highly adipogenic but poorly spread calreticulindeficient ES cells We conclude that forced cell rounding via cytoskeletal disruption overrides the effects of calreticulin an ER chaperone thus negatively regulating adipogenesis via focal adhesionmediated cell spreading
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