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

This is the authors' abstract. We don't add key points for this paper.

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.