Elsevier

Redox Biology

Volume 22, April 2019, 101156
Redox Biology

Research Paper
Age-related oxidative stress confines damage-responsive Bmi1+ cells to perivascular regions in the murine adult heart

https://doi.org/10.1016/j.redox.2019.101156Get rights and content
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Highlights

  • Bmi1+ cardiac damage-responsive cells are sheltered in areas with low ROS levels.

  • Aging-related oxidative damage confines cardiac Bmi1+ cells to perivascular regions.

  • Microvasculature-derived signals regulate adult Bmi1+ damage-responsive cell behavior.

  • Genetic ROS levels manipulation modifies the percentage and identity of Bmi1+ cells.

Abstract

Adult progenitor cells reside in specialized microenvironments which maintain their undifferentiated cell state and trigger regenerative responses following injury. Although these environments are well described in several tissues, the cellular components that comprise the cardiac environment where progenitor cells are located remain unknown. Here we use Bmi1CreERT and Bmi1GFP mice as genetic tools to trace cardiac damage-responsive cells throughout the mouse lifespan. In adolescent mice, Bmi1+ damage-responsive cells are broadly distributed throughout the myocardium. In adult mice, however, Bmi1+ cells are confined predominately in perivascular areas with low levels of reactive oxygen species (ROS) and their number decline in an age-dependent manner. In vitro co-culture experiments with endothelial cells supported a regulatory role of the endothelium in damage-responsive cell behavior. Accordingly, in vivo genetic decrease of ROS levels in adult heart disengaged Bmi1+ cells from the cardiovascular network, recapitulating an adolescent-like Bmi1 expression profile. Thus, we identify cardiac perivascular regions as low-stress microenvironments that favor the maintenance of adult damage-responsive cells.

Keywords

Bmi1
Damage-responsive cell
Vasculature
Oxidative damage
Reactive oxygen species

Cited by (0)

1

D.H. and S.C. contributed equally to this study.