P-SELECTIN EXPRESSION MARKS ACTIVE AND MYELOID-BIASED HEMATOPOIETIC STEM CELLS AND IS UP-REGULATED WITH AGE

Hematopoietic stem cells (HSCs) contribute to blood formation throughout the entire lifespan of an organism, while simultaneously sustaining the stem cell pool. Aged HSCs increase in number while the functional activity of aged HSCs associated with a skewed differentiation potential decreases substantially compared to their young counterparts. Multiple studies have reported that P-selectin (Selp) is consistently upregulated in murine aged HSCs. However, the role of Selp in HSCs aging is not clear. Selp preferentially marks CD150high Lin-Sca-1+ckit+CD48- HSCs, which are myeloid-biased. Beyond an increase of the expression levels of Selp by aged HSCs, the number of Selp+ HSCs expands strongly with age. We in vivo pulsed HSCs using the TetOP-H2B-GFP mouse model in which quiescent HSCs retain the GFP label after an extended chase period. We found that label-retaining GFP+ HSCs show low Selp expression, while more active GFP- HSCs are Selp+. To further investigate functional differences between Selp- and Selp+ HSCs, we separated these two populations from aged donor mice, and transplanted them into lethally irradiated recipients. Preliminary data show that Selp+ HSCs are more myeloid-biased, which is in line with high Selp expression on CD150high HSCs. Therefore, we suggest that Selp- HSCs isolated from an aged donor are functionally 'younger' stem cells. We are currently performing RNA-seq on Selp- and Selp+ aged HSCs to provide further molecular insight into the functional differences between these two highly related, yet differentially aged HSC subsets.