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

Bastiaan C. Du Pré; Evelyne J. Demkes; Dries A.M. Feyen; Pieterjan Dierickx; Sandra Crnko; Bart G. J. M. Kok; Joost P.G. Sluijter; Pieter A. Doevendans; Marc A. Vos; Toon A.B. Van Veen; Linda W. Van Laake

doi:10.1016/j.stemcr.2017.07.010

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

Bastiaan C. Du Pré, Evelyne J. Demkes, Dries A.M. Feyen, Pieterjan Dierickx, Sandra Crnko, Bart G. J. M. Kok, Joost P.G. Sluijter, Pieter A. Doevendans, Marc A. Vos, Toon A.B. Van Veen, Linda W. Van Laake^*

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	762-769
Number of pages	8
Journal	Stem Cell Reports [E]
Volume	9
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2017.07.010
Publication status	Published - 12 Sept 2017

Keywords

circadian rhythm
clock
heart
progenitor cell
SCA1
stem cell

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10.1016/j.stemcr.2017.07.010

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Du Pré, B. C., Demkes, E. J., Feyen, D. A. M., Dierickx, P., Crnko, S., Kok, B. G. J. M., Sluijter, J. P. G., Doevendans, P. A., Vos, M. A., Van Veen, T. A. B., & Van Laake, L. W. (2017). SCA1⁺ Cells from the Heart Possess a Molecular Circadian Clock and Display Circadian Oscillations in Cellular Functions. Stem Cell Reports [E], 9(3), 762-769. https://doi.org/10.1016/j.stemcr.2017.07.010

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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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author = "{Du Pr{\'e}}, {Bastiaan C.} and Demkes, {Evelyne J.} and Feyen, {Dries A.M.} and Pieterjan Dierickx and Sandra Crnko and Kok, {Bart G. J. M.} and Sluijter, {Joost P.G.} and Doevendans, {Pieter A.} and Vos, {Marc A.} and {Van Veen}, {Toon A.B.} and {Van Laake}, {Linda W.}",

note = "Funding Information: The authors would like to thank Professor A. Liu (University of Memphis) for sharing the lentiviral BMAL1-dLuc and CRY1-dLuc plasmids. Funding for this work was provided by the Netherlands Organization for Health Research and Development (ZonMW Veni 91612147 ), the Netherlands Heart Foundation (Dekker 2013T056 ), and the Alexandre Suerman program of the UMC Utrecht . We acknowledge the support from Innovation and the Netherlands CardioVascular Research Initiative (CVON): The Dutch Heart Foundation , the Dutch Federation of University Medical Centers , the Netherlands Organization for Health Research and Development , and the Royal Netherlands Academy of Science . Publisher Copyright: {\textcopyright} 2017 The Authors",

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AU - Du Pré, Bastiaan C.

AU - Demkes, Evelyne J.

AU - Feyen, Dries A.M.

AU - Dierickx, Pieterjan

AU - Crnko, Sandra

AU - Kok, Bart G. J. M.

AU - Sluijter, Joost P.G.

AU - Doevendans, Pieter A.

AU - Vos, Marc A.

AU - Van Veen, Toon A.B.

AU - Van Laake, Linda W.

N1 - Funding Information: The authors would like to thank Professor A. Liu (University of Memphis) for sharing the lentiviral BMAL1-dLuc and CRY1-dLuc plasmids. Funding for this work was provided by the Netherlands Organization for Health Research and Development (ZonMW Veni 91612147 ), the Netherlands Heart Foundation (Dekker 2013T056 ), and the Alexandre Suerman program of the UMC Utrecht . We acknowledge the support from Innovation and the Netherlands CardioVascular Research Initiative (CVON): The Dutch Heart Foundation , the Dutch Federation of University Medical Centers , the Netherlands Organization for Health Research and Development , and the Royal Netherlands Academy of Science . Publisher Copyright: © 2017 The Authors

PY - 2017/9/12

Y1 - 2017/9/12

N2 - 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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SCA1⁺ Cells from the Heart Possess a Molecular Circadian Clock and Display Circadian Oscillations in Cellular Functions

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