J Lengefeld - Ins titute of Biotechnology, University of Helsinki; Department ofBiosciences and Nutrition, Karolinska Ins titutet

S tem cells are remarkably small. Whether small size is importantfor s tem cell function is unknown. We find that hematopoietics tem cells (HSCs) enlarge under conditions knownto decrease s tem cell function. This decreased fitness of largeHSCs is due to reduced proliferation and was accompanied byaltered metabolism. Preventing HSC enlargement or reducinglarge HSCs in size averts the loss of s tem cell potential underconditions causing s tem cell exhaus tion. Las t, we show thatmurine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We concludethat small cell size is important for s tem cell function invivo and propose that s tem cell enlargement contributes to theirfunctional decline during aging