MICROPATTERNED HUMAN PLURIPOTENT STEM CELLS FOR MODELING EMBRYONIC TISSUE PATTERNING AND PATHOGENESIS
National University of Singapore, Singapore Singapore Institute for Neurotechnology
Human pluripotent stem cells (hPSCs) have the remarkable differentiation and self-organization ability to mimic early embryonic tissue development. However, hPSC tissue patterning is often spontaneous in conventional spheroid or monolayer cultures, which limits their translation into standardized experimental models for developmental diseases and drug testing. Tissue patterning during embryonic development relies on the spatio-temporal control of soluble and mechanical environmental factors; although there are limited technologies that offer effective environmental control to spatially pattern stem cell fates.
We have recently demonstrated that stem cell micropatterning can generate mechanical gradients via asymmetry in cell-cell and cell-matrix adhesions to direct the spatial organization of hPSC cell fates. Micropatterned hPSCs can undergo spatially organized differentiation and collective cell migration to form 3D ordered mesoendoderm and neuroepithelium structures. The micropatterned mesoendoderm structures were selectively disrupted by teratogenic (birth defect causing) compounds, which exemplifies its applicability as a teratogenic screening platform. In addition, we show that the micropatterned hPSC neuroepithelium structures can be related to neural tube morphogenesis to serve as a disease model for neural tube defects, a common class of human birth defects.