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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:p>Growth hormone (GH) is a key systemic regulator of longitudinal bone growth and is widely used in pediatric endocrinology, including in patients without GH deficiency. Its primary target is the growth plate\u2014a cartilaginous structure driving bone elongation\u2014yet the cellular mechanisms underlying GH action remain incompletely understood. Here, we identify a direct role for GH in regulating a recently defined population of cartilaginous stem cells within the growth plate. Using multiple transgenic mouse models, we show that GH reduces the pool of slow-cycling, label-retaining stem cells by promoting their differentiation into transient progenitors. Clonal and lineage-tracing analyses reveal that these stem cells renew via population asymmetry and that GH promotes their committed cell division, leading to stem cell depletion. Conversely, genetic deletion of the GH receptor in stem cells impairs their ability to generate chondrocytes, confirming a direct GH effect. 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L. Chu Quantitative multicolored deep imaging of human bones reveals a composite osteo-sinusoidal niche for mesenchymal stromal cells. 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