Spontaneous differentiation of human induced pluripotent stem cells to odorant-responsive olfactory sensory neurons

被引：2

作者：

Kikuta, Hirokazu ^{[1
]}

Tanaka, Hidenori ^{[1
]}

Ozaki, Takashi ^{[1
]}

Ito, Junji ^{[1
]}

Ma, Jiaju ^{[1
]}

Moribe, Shinya ^{[1
]}

Hirano, Minoru ^{[1
]}

机构：

[1] Toyota Cent Res & Dev Labs Inc, 41-1 Yokomichi, Nagakute, Aichi 4801192, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2024年 / 719卷

关键词：

Olfactory receptor; Spontaneous differentiation; iPSCs; Olfactory sensory neurons; Olfaction; Functional olfactory response; GLOBOSE BASAL-CELLS; SPECIFICATION; RECEPTORS; PROTEIN;

D O I：

10.1016/j.bbrc.2024.150062

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells (iPSCs), can differentiate into almost all cell types and are anticipated to have significant applications in the field of regenerative medicine. However, there are no reports of successfully directing iPSCs to become functional olfactory sensory neurons (OSNs) capable of selectively receiving odorant compounds. In this study, we employed dual SMAD inhibition and fibroblast growth factor 8 (FGF-8, reported to dictate olfactory fates) along with N-2 and B-27 supplements in the culture medium to efficiently induce the differentiation of iPSCs into neuronal cells with olfactory function through olfactory placode. Temporal gene expression and expression of OSN-specific markers during differentiation indicated that the expression of olfactory marker proteins and various olfactory receptors (ORs), which are markers of mature OSNs, was observed after approximately one month of differentiation culture, irrespective of the differentiation cues, suggesting differentiation into OSNs. Cells that exhibited specific responses to odorant compounds were identified after administering odorant compounds to differentiated iPSC-derived OSNs. This suggests the spontaneous generation of functional OSNs expressing diverse ORs that respond to odorant compounds from iPSCs.

引用

页数：7

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