Emergent Behavior of Stem Cell Aggregates

Chenyi Pan, Chad Glen, Sarah Seals, Nicholas Peterman

Collaborators: Todd McDevitt, (Gladstone), Yuhong Fan (Georgia Tech), Steve Stice (UGA), Calin Belta (BU)

Funding Source: NSF EBICS Science & Technology Center (Roger Kamm, PI)

Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into cell types of all germ lineages, making them a potentially robust cell source for regenerative medicine therapies; however, the fate and behavior of ESCs is difficult to control and predict, which currently limits their potential uses in medicine and industry. One of the approaches to controlling ESC differentiation is to create ESC aggregates. This approach fails to provide the degree of control necessary for regenerative medicine and stem cell bio-manufacturing applications. Models which can predict phenotypic changes of ESCs in 3-D aggregates would be useful in both industrial and laboratory settings. We are applying rules-based modeling to predict ESC differentiation in EBs and the emergent spatial organization that arises from cell-cell contact and soluble cues.

 

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White, D.E., Sylvester J.B., Kinney M.A., Levario T.J., Lu, H., Streelman J.T., McDevitt, T.C., Kemp, M.L. “Quantitative Multivariate Analysis of Dynamic Multicellular Morphogenic Trajectories”, Integrative Biology, DOI:10.1039/c5ib00072f, 2015.

White, D.E., Kinney, M.A., McDevitt, T.C., Kemp, M.L. “Spatial Pattern Dynamics of 3D Stem Cell Differentiation via Rules-Based Computational Modeling”. PLoS Computational Biology, 9(3): e1002952, 2013.

Nair, R., Ngangan, A.V., Kemp, M.L., McDevitt, T.C. “Gene Expression Signatures of Extracellular Matrix and Growth Factors During Embryonic Stem Cell Differentiation”. PLoS One, 7(10): e42580, 2012.