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Stem Cell Reports. 2019 Feb 28. pii: S2213-6711(19)30024-4. doi: 10.1016/j.stemcr.2019.01.022. [Epub ahead of print]

Single-Cell RNA Sequencing of Human Embryonic Stem Cell Differentiation Delineates Adverse Effects of Nicotine on Embryonic Development.

Author information

1
Stanford Cardiovascular Institute, 265 Campus Drive G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA 94305, USA; Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
2
Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.
3
Stanford Cardiovascular Institute, 265 Campus Drive G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA 94305, USA; Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: joewu@stanford.edu.

Abstract

Nicotine, the main chemical constituent of tobacco, is highly detrimental to the developing fetus by increasing the risk of gestational complications and organ disorders. The effects of nicotine on human embryonic development and related mechanisms, however, remain poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of human embryonic stem cell (hESC)-derived embryoid body (EB) in the presence or absence of nicotine. Nicotine-induced lineage-specific responses and dysregulated cell-to-cell communication in EBs, shedding light on the adverse effects of nicotine on human embryonic development. In addition, nicotine reduced cell viability, increased reactive oxygen species (ROS), and altered cell cycling in EBs. Abnormal Ca2+ signaling was found in muscle cells upon nicotine exposure, as verified in hESC-derived cardiomyocytes. Consequently, our scRNA-seq data suggest direct adverse effects of nicotine on hESC differentiation at the single-cell level and offer a new method for evaluating drug and environmental toxicity on human embryonic development in utero.

KEYWORDS:

differentiation; embryonic development; embryonic stem cells; nicotine; single-cell RNA sequencing; smoking

PMID:
30827876
DOI:
10.1016/j.stemcr.2019.01.022
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