A vast stem-progenitor cell pool, richly vascular system, and hybrid ossification drive the daily centimeter-scale elongation of bony antlers.

Bone growth and regeneration remain major clinical challenges. Deer antlers, the fastest-growing mammalian bone, regenerate via endochondral ossification and elongate up to 2 cm per day, far surpassing the ~2 cm annual growth of human growth plates. Here, we systematically mapped the cellular landscape of the antler growth center (AGC) using single-nucleus RNA sequencing, chromatin accessibility profiling, and spatial transcriptomics. The AGC harbors a large stem-progenitor pool that drives rapid elongation through vigorous proliferation supported by paracrine signaling. These proliferative cells exhibit a transcriptional program with intrinsically low tumorigenic potential, associated with apoptotic regulation. The AGC also establishes a vascularized niche that supports robust angiogenesis, sustains accelerated cartilage growth, and enables efficient recruitment of osteogenic cells. Notably, antlers employ a hybrid ossification strategy, combining endochondral ossification with direct hypertrophic chondrocyte-to-osteoblast transdifferentiation, likely via PHEX⁺ intermediates. Collectively, these findings refine fundamental concepts of endochondral ossification and offer insights for regenerative bone therapies.