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Related Concept Videos

Genetic Screens02:46

Genetic Screens

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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
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RosetteArray® Platform for Quantitative High-Throughput Screening of Human Neurodevelopmental Risk.

Brady F Lundin1,2,3, Gavin T Knight3,4, Nikolai J Fedorchak4

  • 1Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA.

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|May 27, 2024
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Summary
This summary is machine-generated.

The RosetteArray platform offers a scalable method for studying human neurodevelopmental disorders using neural organoids. This 96-well plate assay enables high-throughput screening for drug discovery and understanding disease causes.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Stem Cell Biology

Background:

  • Neural organoids are valuable tools for studying human neurodevelopmental disorders (NDDs).
  • Current limitations include a lack of scalable and quantifiable formats for NDD research and drug discovery.
  • Standardized methods are needed to assess complex NDD etiologies.

Purpose of the Study:

  • To introduce and validate the RosetteArray platform for standardized neural organoid derivation.
  • To demonstrate the platform's utility in screening factors contributing to NDDs and neural tube defects.
  • To enable quantitative high-throughput screening (qHTS) for neurodevelopmental risk assessment.

Main Methods:

  • Utilized the RosetteArray platform, a 96-well plate assay for micropatterned neural rosette tissue generation.
  • Seeded RosetteArrays from cryopreserved human pluripotent stem cells.
  • Cultured organoids for 6-8 days and quantified results using AI-based software analysis of immunostained images.

Main Results:

  • Successfully generated >9000 singularly polarized neural rosette tissues per plate.
  • Demonstrated the platform's effectiveness in screening developmental neurotoxicity.
  • Showcased suitability for assessing genetic and environmental risk factors for neural tube defects.

Conclusions:

  • The RosetteArray platform provides a standardized, scalable, and quantifiable method for neural organoid research.
  • It facilitates high-throughput screening for NDDs, developmental neurotoxicity, and risk factors.
  • This platform holds potential for regulatory applications and precision medicine in neurodevelopmental disorders.