Abstract
Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.
Highlights
Postnatal cell fates are determined by adult stem cells residing in regenerative tissues
Our studies strongly suggest that incisor-specific adult stem cells and their regeneration process are required for ectopic hair formation in Med1 KO mice because 1) hairs are formed only in the incisors but not in the molars, 2) hairs are generated at the expense of enamel, and 3) hairs are post-natally generated and continuously regenerated even after hairs are depilated
Mouse incisors continuously grow throughout their life because of the adult stem cells residing in the cervical loop (CL)
Summary
Postnatal cell fates are determined by adult stem cells residing in regenerative tissues. Dental epithelial stem cells (DE-SC) residing in the labial cervical loop (CL) continuously regenerate dental epithelia in the incisor throughout the life of the mouse. DE-SCs share several characteristics with other adult stem cells in regenerative tissues such as slow division, discrete niche, and the ability to differentiate [1,2]. DE-SCs are supported by a microenvironment within the CL, called the stem cell niche, that plays an important role in maintenance, proliferation, differentiation, and cell fate decisions during dental development [3] as observed in other self-renewing tissues [4]. DE-SCs give rise to all the dental epithelia including the inner and outer enamel epithelia (IEE, called the inner dental epithelium [IDE], and OEE, respectively), the stellate reticulum (SR), the stratum intermedium (SI), and ameloblasts. At the Mat stage, the dental papillary layer is invaded by the vasculature, which provides calcium for enamel mineralization [7]
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