Tissue morphology influences the temporal program of human brain organoid development

• DOI: 10.1016/j.stem.2023.09.003
• Publication Date: 2023-10-05T14:32:21Z
• Authors: Ilaria Chiaradia; Ivan Imaz-Rosshan...; Benedikt S. Nilges; Jerome Boulanger; Laura Pellegrini; Richa Das; Nachiket D. Kashikar; Madeline A. Lanca...
• Keywords: Organoid; Cytoarchitecture; Cell fate determination; Developmental Biology

Progression through fate decisions determines cellular composition and tissue architecture, but how that same architecture may impact cell is less clear. We took advantage of organoids as a tractable model to interrogate this interaction form fate. Screening methodological variations revealed common protocol adjustments impacted various aspects morphology, from macrostructure architecture. examined the morphological perturbations on integrated single nuclear RNA sequencing (snRNA-seq) spatial transcriptomics. Regardless specific protocol, with more complex morphology better mimicked in vivo human fetal brain development. Organoids perturbed displayed aberrant temporal progression, cells being intermingled both space time. Finally, encapsulation impart simplified led disrupted cytoarchitecture similar abnormal maturational timing. These data demonstrate developing require proper coordinates undergo correct progression.