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

Hongchao Guo1, Lei Tian1, Joe Z Zhang1

  • 1Stanford 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.

Stem Cell Reports
|March 5, 2019
PubMed

Insights

Nicotine exposure harms developing fetuses by disrupting cell communication and function. This study reveals nicotine

Area of Science:

  • Developmental Biology
  • Toxicology
  • Stem Cell Biology

Background:

  • Nicotine, a primary tobacco component, poses significant risks to fetal development, including gestational complications and organ damage.
  • The precise mechanisms by which nicotine impacts human embryonic development remain largely unelucidated.

Purpose of the Study:

  • To investigate the effects of nicotine on human embryonic development at the single-cell level.
  • To identify nicotine-induced molecular and cellular changes in human embryonic stem cell-derived embryoid bodies (EBs).

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) was employed on human embryonic stem cell (hESC)-derived EBs exposed to nicotine.
  • Cell viability, reactive oxygen species (ROS) levels, cell cycling, and calcium (Ca2+) signaling were assessed.

Main Results:

  • Nicotine exposure induced lineage-specific responses and disrupted cell-to-cell communication within EBs.
  • Reduced cell viability, increased ROS production, and altered cell cycling were observed in nicotine-treated EBs.
  • Abnormal Ca2+ signaling was detected in muscle cells and hESC-derived cardiomyocytes following nicotine exposure.

Conclusions:

  • Nicotine exerts direct adverse effects on hESC differentiation, impacting embryonic development at a single-cell resolution.
  • The findings provide a novel single-cell-level understanding of nicotine's toxicity on human embryonic development.
  • This study offers a new methodological approach for assessing the in utero toxicity of drugs and environmental factors.

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