4.6 Article

Extension of retinofugal projections in an assembled model of human pluripotent stem cell-derived organoids

期刊

STEM CELL REPORTS
卷 16, 期 9, 页码 2228-2241

出版社

CELL PRESS
DOI: 10.1016/j.stemcr.2021.05.009

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资金

  1. National Eye Institute [R01 EY024984, R21 EY031120]
  2. BrightFocus Foundation [G2020369]
  3. Indiana Department of Health Spinal Cord and Brain Injury Research Fund [26343]
  4. Indiana CTSI predoctoral research fellowship from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award [UL1TR002529]

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By generating in vitro models consisting of retinal organoids, cortical and thalamic organoids, researchers have successfully simulated the projections of the human visual system. This approach not only enhances RGC survival in long-term models but also facilitates studies on human visual system development and related diseases.
The development of the visual system involves the coordination of spatial and temporal events to specify the organization of varied cell types, including the elongation of axons from retinal ganglion cells (RGCs) to post-synaptic targets in the brain. Retinal organoids recapitulate many features of retinal development, yet have lacked downstream targets into which RGC axons extend, limiting the ability to model projections of the human visual system. To address these issues, retinal organoids were generated and organized into an in vitro assembloid model of the visual system with cortical and thalamic organoids. RGCs responded to environmental cues and extended axons deep into assembloids, modeling the projections of the visual system. In addition, RGC survival was enhanced in long-term assembloids, overcoming prior limitations of retinal organoids in which RGCs are lost. Overall, these approaches will facilitate studies of human visual system development, as well as diseases or injuries to this critical pathway.

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