Single-Cell RNA Sequencing of Human Embryonic Stem Cell Differentiation Delineates Adverse Effects of Nicotine on Embryonic Development
AffiliationUniv Arizona, Dept Basic Med Sci, Coll Med, Phoenix
embryonic stem cells
single-cell RNA sequencing
MetadataShow full item record
CitationGuo, H., Tian, L., Zhang, J. Z., Kitani, T., Paik, D. T., Lee, W. H., & Wu, J. C. (2019). Single-Cell RNA Sequencing of Human Embryonic Stem Cell Differentiation Delineates Adverse Effects of Nicotine on Embryonic Development. Stem cell reports, 12(4), 772-786.
JournalSTEM CELL REPORTS
Rights© 2019 The Authors. This is an open access article under the CC BY-NC-ND license.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractNicotine, 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.
NoteOpen access journal
VersionFinal published version
SponsorsNational Institutes of Health (NIH) [T32 EB009035, TRDRP 26FT-0029]; Burroughs Wellcome Fund [1015009, R01 HL130020, R01 HL113006, R01 HL141371, R01 HL132875, TRDRP 27IR-0012]
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