SCA1+ Cells from the Heart Possess a Molecular Circadian Clock and Display Circadian Oscillations in Cellular Functions

Summary Stem cell antigen 1-positive (SCA1+) cells (SPCs) have been investigated in cell-based cardiac repair and pharmacological research, although improved cardiac function after injection has been variable and the mode of action remains unclear. Circadian (24-hr) rhythms are biorhythms regulated by molecular clocks that play an important role in (patho)physiology. Here, we describe (1) the presence of a molecular circadian clock in SPCs and (2) circadian rhythmicity in SPC function. We isolated SPCs from human fetal heart and found that these cells possess a molecular clock based on typical oscillations in core clock components BMAL1 and CRY1. Functional analyses revealed that circadian rhythmicity also governs SPC proliferation, stress tolerance, and growth factor release, with large differences between peaks and troughs. We conclude that SPCs contain a circadian molecular clock that controls crucial cellular functions. Taking circadian rhythms into account may improve reproducibility and outcome of research and therapies using SPCs.
Highlights • SCA1+ cells are a cell source used in pharmacology studies and cardiac repair • SCA1+ cells possess a molecular circadian (24-hr) clock • Proliferation, stress tolerance, and paracrine secretion follow a circadian pattern • Taking rhythmicity into account may improve studies using SCA1+ cells
SCA1+ cells (SPCs) have been used for pharmacological studies and cell-based cardiac repair. Van Laake and colleagues isolated human SPCs and demonstrated that these cells possess molecular circadian clocks. Functional analyses revealed circadian rhythmicity in SPC proliferation, stress tolerance, and growth factor release. Their findings could improve reproducibility, translation, and outcome of studies using SPCs and other progenitor-like cells.