Dendritic spine formation and synapse maturation in transcription factor-induced human iPSC-derived neurons

• Published in: iScience Vol. 26; no. 4; p. 106285
• Main Authors: Lin, Waka, Shiomoto, Shusaku, Yamada, Saki, Watanabe, Hikaru, Kawashima, Yudai, Eguchi, Yuichi, Muramatsu, Koichi, Sekino, Yuko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.04.2023; Elsevier
• Subjects: Cell biology; Neuroscience; Stem cells research; Cell biology; Neuroscience; Stem cells research
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106285

Synaptic maturation is reportedly limited in human induced pluripotent stem cell (iPSC)-derived neurons. Notably, their ability to reach postnatal-like stages and form dendritic spines has been difficult to demonstrate unless using long-term cultured organoids. Recent transcription factor (TF)-based induction methods allow the accelerated generation of differentiated neurons, which offers an unprecedented opportunity to address further progression into late developmental stages. Herein, we report on a comprehensive time-course study of TF-induced iPSC neurons cultured in vitro through an intrinsic maturation program following neurogenesis. Moreover, we determined the transcriptional and morphological sequences of key developmental events associated with spinogenesis, including the conversion of drebrin to its brain-specific isoform A and the N-methyl-D-aspartate (NMDA) receptor subunit switch. TF-induced iPSC neurons successfully acquired structural and functional synaptic maturity, which will critically expand their utility in modeling higher brain functions and disorders. [Display omitted] •Synaptic maturation and spinogenesis of cultured human iPSC-derived neurons•TF-induced iPSC neurons reproduce postnatal brain development features•Robust dendritic spine formation is shown by drebrin A expression and localization•TF-induced iPSC neurons acquire mature functions underlying synaptic plasticity Cell biology; Neuroscience; Stem cells research