A single-cell transcriptomic atlas identifies key progenitor populations driving postnatal horn bud development in goats (Capra hircus)

Ruminant headgear represents a hallmark of adaptive morphological innovation, yet the cellular programs driving postnatal horn development remain unclear. Here, we integrate histological, bulk, and single-cell transcriptomic analyses to construct a cellular atlas of goat horn bud morphogenesis. We identify a critical transition at postnatal day 7, marked by dermal ossification and epidermal thickening. Dermal lineage cells (DLCs) undergo sharp expansion and osteogenic activation, while epidermal lineage cells (ELCs) shift toward collagen remodeling and mineralized cornification. Notably, we uncover ZEB2+ horn bud progenitor mesenchymal cells (ZEB2+PMCs) that initiate horn-specific osteogenesis via mesenchymal-to-osteogenic transition. Functional assays confirm their robust osteogenic potential in vitro and in vivo. Concurrently, proliferative basal keratinocytes give rise to spinous cells, which interact with osteogenic cells via SPP1 signaling to promote sheath mineralization. Cross-species analysis reveals conserved progenitor mesenchymal cell driven osteogenesis in horn and antler, while keratinocyte programs diverge. These findings uncover coordinated dermal and epidermal mechanisms driving horn morphogenesis and offer insight into the evolution of cranial appendages in ruminants. Single-cell analysis of goat horn buds reveals a day 7 developmental switch in which ZEB2+ progenitor mesenchymal cells initiate osteogenesis while keratinocytes drive sheath mineralization, defining coordinated dermal–epidermal programs of ruminant headgear formation.