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MolES Seminar: Dr. Todd McDevitt (Gladstone Institutes)
MolES Seminar: Dr. Todd McDevitt (Gladstone Institutes)
WhenTuesday, Feb 4, 2020, 1 – 2 p.m.
Campus locationMolecular Engineering (MOL)
Campus roomNanoES 181
Event typesLectures/Seminars
Event sponsorsMolecular Engineering and Sciences

Molecular Engineering and Sciences Seminar Series
Abstract: Engineering endogenous molecular pathways to direct emergent properties of pluripotent stem cells

The creation of organoids from pluripotent stem cells requires the co-emergence of multiple cell types in a spatially and temporally coordinated fashion. However, co-emergence is not precisely controlled due to an inability to reliably manipulate divergent events via endogenous molecular pathways. In order to control early symmetry breaking events prior to the onset of phenotypic changes, we have modulated gene expression within sub-populations of human induced pluripotent stem cells (hiPSCs) using an inducible CRISPR interference system. Mosaic colonies of hiPSCs exhibited different types of multicellular patterns depending upon the timing and dosing of silencing specific genes, in addition to the proportion of cells experiencing gene knock-down. The resulting behaviors of hiPSCs under pluripotent and differentiation conditions (i.e. BMP4, dual SMAD inhibition) were tracked using a neural network trained to segment individual cells and quantify their movement in high density, epithelial colonies. The neural network detection enabled identification of hiPSC collective migration and condensation events that preceded differentiation. The kinetics of gene silencing and cell movement data were used to create a Cellular Potts computational model capable of accurately modeling multicellular organization and subsequently optimized with machine learning to predict different spatial patterns. In vitro experiments using identical starting conditions for mosaic hiPSC colonies accurately recreated the predicted multicellular patterns, thus “closing the loop” between in silico and in vitro systems. These results demonstrate how the emergent properties of PSC self-organization and divergent cell phenotypes can be controlled as a first step towards engineering more robust methods for organoid development.
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty.…
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