TY - JOUR TI - Leptin receptor, a surface marker for a subset of highly engrafting long-term functional hematopoietic stem cells AU - Trinh, Thao AU - Ropa, James AU - Aljoufi, Arafat AU - Cooper, Scott AU - Sinn, Anthony AU - Srour, Edward F. AU - Broxmeyer, Hal E. T2 - Leukemia AB - The hematopoietic system is sustained by a rare population of hematopoietic stem cells (HSCs), which emerge during early embryonic development and then reside in the hypoxic niche of the adult bone marrow microenvironment. Although leptin receptor (Lepr)-expressing stromal cells are well-studied as critical regulators of murine hematopoiesis, the biological implications of Lepr expression on HSCs remain largely unexplored. We hypothesized that Lepr+HSCs are functionally different from other HSCs. Using in vitro and in vivo experimental approaches, we demonstrated that Lepr further differentiates SLAM HSCs into two distinct populations; Lepr+HSCs engrafted better than Lepr−HSCs in primary transplant. Compared to Lepr−LSK cells, Lepr+LSK cells were highly enriched for extensively repopulating and self-renewing HSCs. Molecularly, Lepr+HSCs were characterized by a pro-inflammatory transcriptomic profile enriched for Type-I Interferon and Interferon-gamma (IFN-γ) response pathways, which are known to be critical for the emergence of HSCs in the embryo. We conclude that although Lepr+HSCs represent a minor subset of HSCs, they are highly engrafting cells that possess embryonic-like transcriptomic characteristics, and that Lepr can serve as a reliable marker for functional long-term HSCs, which may have potential clinical applicability. DA - 2020/11/07/ PY - 2020 DO - 10.1038/s41375-020-01079-z DP - www.nature.com SP - 1 EP - 12 LA - en SN - 1476-5551 UR - https://www.nature.com/articles/s41375-020-01079-z Y2 - 2020/11/09/18:10:48 ER -