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Age-related changes in the hematopoietic stem cell pool revealed via quantifying the balance of symmetric and asymmetric divisions.

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Kawahigashi, Teiko 
Takahashi, Munetomo 
Bhadury, Joydeep 
Iwami, Shingo 


Hematopoietic stem cells (HSCs) are somatic stem cells that continuously generate lifelong supply of blood cells through a balance of symmetric and asymmetric divisions. It is well established that the HSC pool increases with age. However, not much is known about the underlying cause for these observed changes. Here, using a novel method combining single-cell ex vivo HSC expansion with mathematical modeling, we quantify HSC division types (stem cell-stem cell (S-S) division, stem cell-progenitor cell (S-P) division, and progenitor cell-progenitor cell (P-P) division) as a function of the aging process. Our time-series experiments reveal how changes in these three modes of division can explain the increase in HSC numbers with age. Contrary to the popular notion that HSCs divide predominantly through S-P divisions, we show that S-S divisions are predominant throughout the lifespan of the animal, thereby expanding the HSC pool. We, therefore, provide a novel mathematical model-based experimental validation for reflecting HSC dynamics in vivo.


Acknowledgements: We thank the University of Tokyo Institute of Medical Science (IMSUT) FACS core laboratory for expert technical assistance.


Animals, Cell Division, Hematopoietic Stem Cells, Cell Cycle, Cell Proliferation, Models, Theoretical, Cell Differentiation

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PLoS One

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Public Library of Science (PLoS)