Issue 6, 2018

Human brain organoid-on-a-chip to model prenatal nicotine exposure

Abstract

Nicotine has been recognized to trigger various neuronal disabilities in the fetal brain and long-lasting behavioral deficits in offspring. However, further understanding of fetal brain development under nicotine exposure is challenging due to the limitations of existing animal models. Here, we create a new brain organoid-on-a-chip system derived from human induced pluripotent stem cells (hiPSCs) that allows us to model neurodevelopmental disorders under prenatal nicotine exposure (PNE) at early stages. The brain organoid-on-a-chip system facilitates 3D culture, in situ neural differentiation, and self-organization of brain organoids under continuous perfused cultures in a controlled manner. The generated brain organoids displayed well-defined neural differentiation, regionalization, and cortical organization, which recapitulates the key features of the early stages of human brain development. The brain organoids exposed to nicotine exhibited premature neuronal differentiation with enhanced expression of the neuron marker TUJ1. Brain regionalization and cortical development were disrupted in the nicotine-treated organoids identified by the expressions of forebrain (PAX6 and FOXG1), hindbrain (PAX2 and KROX20) and cortical neural layer (preplate TBR1 and deep-layer CTIP2) markers. Moreover, the neurite outgrowth showed abnormal neuronal differentiation and migration in nicotine-treated brain organoids. These results suggest that nicotine exposure elicits impaired neurogenesis in early fetal brain development during gestation. The established brain organoid-on-a-chip system provides a promising platform to model neurodevelopmental disorders under environmental exposure, which can be extended for applications in brain disease studies and drug testing.

Graphical abstract: Human brain organoid-on-a-chip to model prenatal nicotine exposure

Supplementary files

Article information

Article type
Paper
Submitted
09 10月 2017
Accepted
06 2月 2018
First published
07 2月 2018

Lab Chip, 2018,18, 851-860

Human brain organoid-on-a-chip to model prenatal nicotine exposure

Y. Wang, L. Wang, Y. Zhu and J. Qin, Lab Chip, 2018, 18, 851 DOI: 10.1039/C7LC01084B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements