Bone marrow adipoq-lineage cells in regulating the bone and marrow microenvironment: identities, functions, and mechanisms.

Bone marrow Adipoq-lineage cells refer to all cells that have ever expressed Adipoq (Adiponectin) and their progeny. They contribute not only to marrow adipogenesis but also to osteoclast regulation, hematopoietic support, vascular maintenance, and post-injury regeneration. Recent single-cell transcriptomic and genetic fate-mapping studies have revealed unexpected heterogeneity within this lineage, such as genuine adipogenic precursors (MALPs), bipotent adipo-osteoprogenitors (Adipoq+Osx+ cells), and their differentiated progeny (including mature marrow adipocytes and, in some contexts, osteoblasts). The progenitor subsets partly overlap with well-characterized SSPC subsets such as CXCL12-abundant reticular cells and leptin receptor-expressing cells, yet they exhibit distinct functional properties. This review synthesizes current knowledge on the identity, differentiation potential, and multifaceted functions of bone marrow Adipoq-lineage cells, with a focus on their roles in promoting osteoclastogenesis, regulating osteogenesis, supporting hematopoiesis and vascular integrity, and mediating bone marrow repair after injury. We also discuss how these cells are regulated by intrinsic factors that either control cell-autonomous fate or modulate secretory phenotype, and highlight key unresolved questions. By integrating these findings into a unified conceptual framework, this review aims to guide future research and therapeutic development targeting these cells in skeletal and hematopoietic disorders.