SUMMARYDynamical control of the cellular microenvironment is highly desired for quantitative studies of stem cells and immune signaling. Here, we present an automated microfluidic system for high-throughput culture, differentiation and analysis of a wide range of cells in precisely defined dynamic microenvironments recapitulating cellular niches. This system delivers complex, time-varying biochemical signals to 1,500 independently programmable cultures containing either single cells, 2-D populations, or 3-D organoids, and dynamically stimulates adherent or non-adherent cells while tracking and retrieving them for end-point analysis. Using this system, we investigated the signaling landscape of neural stem cell differentiation under combinatorial and dynamic stimulation with growth factors. Experimental and computational analyses identified "cellular logic rules" for stem cell differentiation, and All rights reserved. No reuse allowed without permission.
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