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Published on: September 27, 2012
SCA1+ Cells from the Heart Possess a Molecular Circadian Clock and Display Circadian Oscillations in Cellular
Bastiaan C Du Pré1, Evelyne J Demkes1, Dries A M Feyen2
1Department of Medical Physiology, Division of Heart and Lungs, and Regenerative Medicine Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Department of Cardiology, Division of Heart and Lungs, and Regenerative Medicine Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Insights
Stem cell antigen 1-positive cells possess a molecular circadian clock. This internal clock regulates key cell functions, potentially improving cardiac repair research and therapies.
Area of Science:
- Cardiovascular Biology
- Chronobiology
- Stem Cell Research
Background:
- Stem cell antigen 1-positive cells (SPCs) are explored for cardiac repair, but outcomes are inconsistent and mechanisms are unclear.
- Circadian rhythms, regulated by molecular clocks, significantly influence physiological and pathological processes.
Purpose of the Study:
- To investigate the presence and function of a molecular circadian clock within SPCs.
- To determine if circadian rhythms impact SPC functions relevant to cardiac repair.
Main Methods:
- Isolation of SPCs from human fetal heart tissue.
- Analysis of core clock gene expression (e.g., BMAL1, CRY1) for molecular clock confirmation.
- Functional assays assessing SPC proliferation, stress tolerance, and growth factor release under circadian control.
Main Results:
- SPCs were confirmed to possess a molecular circadian clock, evidenced by oscillating core clock components.
- Circadian rhythmicity was found to significantly influence SPC proliferation, stress tolerance, and growth factor secretion.
- Substantial variations in these cellular functions were observed between peak and trough times of the circadian cycle.
Conclusions:
- SPCs harbor an intrinsic circadian molecular clock that governs critical cellular functions.
- Incorporating circadian dynamics into SPC research and therapeutic strategies may enhance reproducibility and efficacy in cardiac repair.
Abstract:
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.
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