Trinh, ThaoRopa, JamesAljoufi, ArafatCooper, ScottSinn, AnthonySrour, Edward F.Broxmeyer, Hal E.2024-08-062024-08-062021Trinh T, Ropa J, Aljoufi A, et al. Leptin receptor, a surface marker for a subset of highly engrafting long-term functional hematopoietic stem cells. Leukemia. 2021;35(7):2064-2075. doi:10.1038/s41375-020-01079-zhttps://hdl.handle.net/1805/42657The 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 and self-renewed more extensively as noted in secondary transplants. Molecularly, Lepr+HSCs were characterized by a proinflammatory 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.en-USPublisher PolicyLeptin receptorHematopoietic stem cellsHematopoietic cell transplantationArticle