Browsing by Subject "Auditory"

Now showing 1 - 3 of 3
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    Chemically defined and dynamic click hydrogels support hair cell differentiation in human inner ear organoids
    (Elsevier, 2025) Arkenberg, Matthew R.; Jafarkhani, Mahboubeh; Lin, Chien-Chi; Hashino, Eri; Otolaryngology -- Head and Neck Surgery, School of Medicine
    The mechanical properties in the inner ear microenvironment play a key role in its patterning during embryonic development. To recapitulate inner ear development in vitro, three-dimensional tissue engineering strategies including the application of representative tissue models and scaffolds are of increasing interest. Human inner ear organoids are a promising model to recapitulate developmental processes; however, the current protocol requires Matrigel that contains ill-defined extracellular matrix components. Here, we implement an alternative, chemically defined, dynamic hydrogel to support the differentiation of human inner ear organoids. Specifically, thiol-norbornene and hydrazide-aldehyde click chemistries are used to fabricate inner ear organoid-laden, gelatin-based scaffolds. We identify optimal formulations to support hair cell development with comparable efficiency and fidelity to Matrigel-cultured organoids. These results suggest that the chemically defined hydrogel may serve as a viable alternative to Matrigel for inner ear tissue engineering.
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    Generating high-fidelity cochlear organoids from human pluripotent stem cells
    (Elsevier, 2023) Moore, Stephen T.; Nakamura, Takashi; Nie, Jing; Solivais, Alexander J.; Aristizábal-Ramírez, Isabel; Ueda, Yoshitomo; Manikandan, Mayakannan; Reddy, V. Shweta; Romano, Daniel R.; Hoffman, John R.; Perrin, Benjamin J.; Nelson, Rick F.; Frolenkov, Gregory I.; Chuva de Sousa Lopes, Susana M.; Hashino, Eri; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Mechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by genetic mutations and environmental insults. The paucity of human cochlear tissues makes it difficult to study cochlear hair cells. Organoids offer a compelling platform to study scarce tissues in vitro; however, derivation of cochlear cell types has proven non-trivial. Here, using 3D cultures of human pluripotent stem cells, we sought to replicate key differentiation cues of cochlear specification. We found that timed modulations of Sonic Hedgehog and WNT signaling promote ventral gene expression in otic progenitors. Ventralized otic progenitors subsequently give rise to elaborately patterned epithelia containing hair cells with morphology, marker expression, and functional properties consistent with both outer and inner hair cells in the cochlea. These results suggest that early morphogenic cues are sufficient to drive cochlear induction and establish an unprecedented system to model the human auditory organ.
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    Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome
    (Elsevier, 2025) Ward, Heather Burrell; Beermann, Adam; Xie, Jing; Yildiz, Gulcan; Felix, Karlos Manzanarez; Addington, Jean; Bearden, Carrie E.; Cadenhead, Kristin; Cannon, Tyrone D.; Cornblatt, Barbara; Keshavan, Matcheri; Mathalon, Daniel; Perkins, Diana O.; Seidman, Larry; Stone, William S.; Tsuang, Ming T.; Walker, Elaine F.; Woods, Scott; Coleman, Michael J.; Bouix, Sylvain; Holt, Daphne J.; Öngür, Dost; Breier, Alan; Shenton, Martha E.; Heckers, Stephan; Halko, Mark A.; Lewandowski, Kathryn E.; Brady, Roscoe O., Jr.; Psychiatry, School of Medicine
    Background: Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future. Methods: The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study-identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants. Results: Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132). Conclusions: This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.