Engineering induction of singular neural rosette emergence within hPSC-derived tissues

• Published in: eLife Vol. 7
• Main Authors: Knight, Gavin T, Lundin, Brady F, Iyer, Nisha, Ashton, Lydia Mt, Sethares, William A, Willett, Rebecca M, Ashton, Randolph Scott
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 29.10.2018; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: advanced biomanufacturing; Algorithms; Anencephaly; Artificial intelligence; Biophysical Phenomena; Brain; Cell Differentiation; Central nervous system; Contractility; Cysts; Displays (Marketing); Engineering; Forebrain; Gene expression; human pluripotent stem cells; Humans; Immunoglobulins; Morphogenesis; Morphology; neural rosette; Neural stem cells; Neurons; Neuroscience; Organ Culture Techniques - methods; organoid morphogenesis; Organoids; Physiological aspects; Pluripotency; Pluripotent Stem Cells - physiology; Prosencephalon - cytology; Spinal Cord - cytology; stem cell bioengineering; Stem cells; Stem Cells and Regenerative Medicine; United States > US; Germany; stem cells; advanced biomanufacturing; stem cell bioengineering; neural stem cells; neural rosette; neuroscience; regenerative medicine; organoid morphogenesis; human pluripotent stem cells; human
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.37549

Human pluripotent stem cell (hPSC)-derived neural organoids display unprecedented emergent properties. Yet in contrast to the singular neuroepithelial tube from which the entire central nervous system (CNS) develops in vivo, current organoid protocols yield tissues with multiple neuroepithelial units, a.k.a. neural rosettes, each acting as independent morphogenesis centers and thereby confounding coordinated, reproducible tissue development. Here, we discover that controlling initial tissue morphology can effectively (>80%) induce single neural rosette emergence within hPSC-derived forebrain and spinal tissues. Notably, the optimal tissue morphology for observing singular rosette emergence was distinct for forebrain versus spinal tissues due to previously unknown differences in ROCK-mediated cell contractility. Following release of geometric confinement, the tissues displayed radial outgrowth with maintenance of a singular neuroepithelium and peripheral neuronal differentiation. Thus, we have identified neural tissue morphology as a critical biophysical parameter for controlling in vitro neural tissue morphogenesis furthering advancement towards biomanufacture of CNS tissues with biomimetic anatomy and physiology.