Laminin 511 and WNT signalling sustain prolonged expansion of hiPSC-derived hippocampal progenitors

Keagan Dunville, Fabrizio Tonelli, Elena Novelli, Azzurra Codino, Verediana Massa, Anna Maria Frontino, Silvia Galfrè, Francesca Biondi, Stefano Gustincich, Matteo Caleo , Luca Pandolfini, Claudia Alia, and Federico Cremisi.

Development, 2022

The authors identify laminin-511 as a crucial laminin isoform for prolonging the neural stem cell (NSC) state and extending hippocampal NSC proliferation for over 200 days in vitro. Biolaminin 511 supported adhesion and cell cycle progression of the dividing hippocampal progenitors. LN511 was crucial in supporting progenitor proliferation, inhibiting differentiation, and sustaining a gene expression profile responsible for maintaining a hippocampal neurogenic niche for extended periods compared with isoforms LN121, LN332, LN441, and with a mouse laminin product. The study involved a novel protocol for differentiating hippocampal NPCs from human induced pluripotent stem cells via a WNT actuator. The differentiation capability of both young and older NPC populations was retained when tested by xenografting into mice.