Journal of Bone and Mineral Metabolism · Feb 19, 2026
Multifunctional LepR⁺ skeletal stem/progenitor cells for bone and marrow homeostasis
By Desai KM, Mizoguchi T
BACKGROUND: Bone is a multifunctional organ that provides structural support and hosts the bone marrow, a key site for hematopoiesis and systemic homeostasis. These dual features have long attracted the attention of both bone biologists and hematologists. Each field has pursued the identification of stem-like cells responsible for hard tissue formation and the regulatory microenvironment/niche that supports hematopoietic stem cells (HSCs), which give rise to all blood cell lineages. Converging advances in bone and hematopoietic biology have led to the identification of skeletal stem/progenitor cells (SSPCs), a multifunctional population that gives rise to osteolineage cells and serves as a principal component of the HSC niche. This landmark discovery was largely enabled by Cre/loxP-based genetic mouse models. Among them, the leptin receptor (LepR)-Cre system has become one of the most widely used tools in skeletal stem cell research worldwide. OBJECTIVE: In this review, we summarize the historical background and recent advances in SSPC research, specifically LepR⁺ SSPCs, highlighting their function and lineage plasticity during development, adolescence, aging, and fracture healing. Advanced genetic labeling-based studies and single-cell transcriptomics unveiled the fate, dynamics and indispensible roles of LepR⁺ SSPCs under both homeostatic and pathological conditions.