RECODE: Spatial engineering of morphogens for the reproducible formation of cortical organoids with arealization

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The human brain is comprised of different regions, including primary, sensory, and motor cortices. These areas are affected in many neurological disorders. It is crucial to reproducibly create brain areas in organoids to better understand early development. This project aims to develop hydrogel-based bioengineering technologies to accurately make different areas of the cerebral cortex in cortical organoids. To accomplish these goals, a multidisciplinary team will leverage expertise in cell and developmental biology, soft materials engineering, and bioinformatics. The broader societal impacts of this project include educational and outreach activities that engage the public and students from underserved communities in partnership with the UCI Stem Cell Research Center, UCI Center for the Neurobiology of Learning and Memory, UCI Office of Access and Inclusion, and OC STEM Initiative. Direct access to human tissue is indispensable for deep understanding of the mechanisms underlying human brain development and disease. Therefore, cortical organoids that closely mimic many aspects of the fetal cortex have emerged as accessible and promising in vitro tools. However, cortical organoids currently lack arealization – the reproducible cellular diversity and distinct spatial organization within the neocortex. To achieve arealization in cortical organoids, a novel responsive hydrogel platform will be developed that can generate spatial patterning of morphogen sources. This platform will be leveraged for examining gene regulatory networks underlying signaling interactions for specifying different areas, using single-cell and spatial transcriptomics. The approaches and insights developed in this project can be applied towards understanding morphogenesis and generating reproducible organoids in other systems beyond cortical organoids. This RECODE project is funded by the Engineering Biology and Health Cluster in the Division of Chemical, Bioengineering, Environmental, and Transport Systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.