epithelial stem cells can milk-producing cells

transplanted into an epithelium-free mammary mesenchyme (also called fat pad) for de novo generation of functional ductal epithelial structures (11, 13). Expansion of the bilayered mammary epithelium occurs under the influence of hormones and is sustained by adult epithelial stem cells (14, 15). Here we aimed to demonstrate for the first time the capacity of DESCs to give rise to non-dental cell lineages that contribute to the formation of epithelial structures in organs other than teeth. Abstract Although dental epithelial stem cells (DESCs) are able to generate all epithelial cell populations within incisors , it remains unclear whether they also have the ability to adopt alternative fates in response to extrinsic factors. We have explored this possibility in the context of mammary gland regeneration. Transplantation of DESCs together with mammary epithelial cells into the mammary stroma allowed the formation of chimeric ductal epithelial structures in which DESCs adopted all the possible mammary fates including milk-producing alveolar cells. However, when DESCs transplanted without mammary epithelial cells they developed branching rudiments and cysts. These in vivo findings demonstrate that when outside their niche, DESCs redirect their fates according to their new microenvironment and thus can contribute to the regeneration of non-dental tissues. we that DESCs can be fully reprogrammed to a mammary epithelial phenotype. DESCs gave rise to all cell types that compose the mammary epithelium, including milk-producing cells. DESCs can form a small ductal system without inputs from mammary epithelium, a characteristic morphogenetic process for many developing organs such as mammary glands, salivary glands and lungs, but not representative of odontogenesis (1). Classic chimeric recombination models demonstrated that the epithelial component is highly malleable and that cell fate and tissue function are strongly influenced by the stromal component of the gland. These studies using the mammary reconstitution assay indeed have shown that also neuronal, testicular, bone marrow and cancer cells mixed together with MECs can be reprogrammed and integrate into the epithelial ductal outgrowths (25-27). However, these non-mammary epithelial cells never showed the ability to grow in mammary stroma without the support of MECs (12) and they were not able to generate ducts (25, 26). The present results provide the first evidence that mammary branching structures can be formed in absence of mammary epithelial inputs. Tooth and mammary gland development display several molecular and morphological similarities in their initial stages. Both organs belong to the class of ectodermal appendages and develop as a result of continuous and reciprocal interactions between epithelium and mesenchyme. The initial stages of mammary and tooth development largely depend on the same molecular cues, mostly associated to transforming growth factor β (Tgf- β ), fibroblast growth factor (Fgf) and Wnt signaling pathways (28, 29). Mutations in genes coding for Wnt ligands lead to similar defects in tooth and mammary development, as they cause tooth agenesis and mammary glands aplasia At later stages however dental and