Aging leads to a decline in function of hematopoietic stem cells (HSCs) and increases susceptibility to hematological disease. We found CD61 to be highly expressed in aged HSCs. Here we investigate the role of CD61 in identifying distinct subpopulations of aged HSCs and assess how expression of CD61 affects stem cell function. We show that HSCs with high expression of CD61 are functionality superior and retain self-renewal capacity in serial transplantations. A population of aged HSCs with highest CD61 expression is functionally comparable to young HSCs. These CD61 High HSCs display a notably higher quiescence compared to their CD61 Low counterparts. We also show that CD61 High and CD61 Low HSCs are transcriptomically distinct populations within aged HSCs. Collectively, our research identifies CD61 as a key player in maintaining stem cell quiescence during aging, ensuring the preservation of their functional integrity and potential. Moreover, CD61 emerges as a marker to prospectively isolate a superior, highly dormant population of young and aged HSCs, making it a valuable tool both in fundamental and clinical research.

Highlights

CD61 expression marks a functionally superior population of long-term hematopoietic stem cells and plays a pivotal role in the maintenance of aged LT-HSCs by regulating their dormancy Aged LT-HSCs with high expression of CD61 are functionally comparable to their young counterparts