Abstract
The continuous growth of rodent incisors is ensured by clusters of mesenchymal and epithelial stem cells that are located at the posterior part of these teeth. Genetic lineage tracing studies have shown that dental epithelial stem cells (DESCs) are able to generate all epithelial cell populations within incisors during homeostasis. However, it remains unclear whether these cells have the ability to adopt alternative fates in response to extrinsic factors. Here, we have studied the plasticity of DESCs in the context of mammary gland regeneration. Transplantation of DESCs together with mammary epithelial cells into the mammary stroma resulted in the formation of chimeric ductal epithelial structures in which DESCs adopted all the possible mammary fates including milk-producing alveolar cells. In addition, when transplanted without mammary epithelial cells, DESCs 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.
Highlights
Ectodermal appendages, such as hair follicles, teeth, salivary and mammary glands, are highly specialized structures that develop through continuous molecular crosstalk between epithelium and mesenchyme
dental epithelial stem cells (DESCs) expressing both epithelial and stem cell markers (Figure 1B, Figure S1) were obtained from the cervical loop of green fluorescent protein (GFP) incisors via a cloning assay. These DESCs were mixed with primary mammary epithelial cells (MECs) and injected into epithelium-free mammary fat pads of immunocompromised
We aimed to assess the plasticity of dental epithelial stem cells (DESCs) and their capacity to contribute to the regeneration of non-dental organs, namely mammary glands
Summary
Ectodermal appendages, such as hair follicles, teeth, salivary and mammary glands, are highly specialized structures that develop through continuous molecular crosstalk between epithelium and mesenchyme. These organs exhibit morphological and regulatory similarities during the earliest stages of development [1,2]. Molecular fine-tuning at more advanced developmental stages defines organ specificity and function. Classical tissue recombination experiments have highlighted the importance of these regulatory signals during ectodermal organ development and revealed that the mesenchyme contains the morphogenetic potential [4,5]. Epithelial cells can be redirected and adopt alternative fates under the influences of tissue-specific mesenchymal signals
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