Stem cell differentiation and the influence of microenvironment<br/><br/><br/><br/>

Monday, September 13, 2010 - 2:15pm - 3:00pm
Lind 305
Dennis Discher (University of Pennsylvania)
Cells make a number of key decisions by actively adhering to a substrate and applying forces. Naive mesenchymal stem cells (MSCs) from human bone marrow will be shown to specify lineage and commit to phenotypes on collagen-coated hydrogels with tissue-level elasticity. Soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of myosin blocks all elasticity directed lineage specification – without strongly perturbing many other aspects of cell function and shape. Physical studies of nuclei suggest an unusual degree of plasticity for stem cell nuclei, and a Cysteine Shotgun Mass Spectrometry method for in situ labeling of the 'foldome' reveals distinct structural differences attributable to unfolding and/or dissociation of cellular proteins. The results have significant implications for understanding physical effects of the in vivo microenvironment and also – as will be shown – for therapeutic uses of stem cells such as in muscle repair.

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