Abstract:
: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.
journal_name
Elifejournal_title
eLifeauthors
Knight GT,Lundin BF,Iyer N,Ashton LM,Sethares WA,Willett RM,Ashton RSdoi
10.7554/eLife.37549subject
Has Abstractpub_date
2018-10-29 00:00:00issn
2050-084Xpii
37549journal_volume
7pub_type
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