The use of organoids has significantly accelerated our understanding of human brain development and disease. The research team showed that Zika infections caused novel reductions in ventricle volume and frequency, and significant differences in the spatial context of rare TBR1+ and SOX2+ cells that are critical for normal brain development. Albanese and colleagues to quantify the impact of Zika virus infection on brain development. In turn, the SCOUT pipeline enabled automated multiscale comparative 3D analyses of whole organoids and was utilized by Dr.
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In the Albanese study, induced pluripotent stem cell-derived cerebral organoids were SHIELD-processed and passively cleared using the multipurpose sample-processing device Eas圜lear. Furthermore, this collaboration led to the development of a novel computational pipeline entitled ‘Single-cell and Cytoarchitecture analysis of Organoids using Unbiased Techniques’ (SCOUT). Lee Gehrke (Massachusetts Institute of Technology/Harvard Medical School, MA) to perform rapid and multiscale phenotyping of intact cerebral organoids using 3D tissue clearing and imaging (see “Multiscale 3D phenotyping of human cerebral organoids”, Scientific Reports, 2020). Paola Arlotta (Harvard University, MA) and Dr. Kwanghun Chung’s laboratory (Massachusetts Institute of Technology, MA) collaborated with Dr. In addition, current organoid mapping depends mainly on single-cell transcriptome analyses and 2D histology. One of the challenges of organoids is the low reproducibility and high heterogeneity across different cultures and experiments, preventing reliable quantitative comparative analyses between conditions. These cells are self-renewing, self-organizing, and able to grow into 3D structures resembling the architecture and physiology of the original biological specimens.ģD organoid models have become indispensable for studying a number of human diseases, including the Zika virus. Organoids are derived either from induced pluripotent or organ-restricted adult stem cells. Emerging organoid technologies have been used to model human organ development and diseases “in a dish”.