Sox10 Regulates Plasticity of Epithelial Progenitors toward Secretory Units of Exocrine Glands

Harleen K. Athwal; George Murphy, III; Ellis Tibbs; Ashley Cornett; Emily Hill; Kenji Yeoh; Elsa Berenstein; Matthew P. Hoffman; Isabelle M.A. Lombaert

Sox10 Regulates Plasticity of Epithelial Progenitors toward Secretory Units of Exocrine Glands

2019

Summary: Understanding how epithelial progenitors within exocrine glands establish specific cell lineages and form complex functional secretory units is vital for organ regeneration. Here we identify the transcription factor Sox10 as essential for both the maintenance and differentiation of epithelial KIT+FGFR2b+ progenitors into secretory units, containing acinar, myoepithelial, and intercalated duct cells. The KIT/FGFR2b-Sox10 axis marks the earliest multi-potent and tissue-specific progenitors of exocrine glands. Genetic deletion of epithelial Sox10 leads to loss of secretory units, which reduces organ size and function, but the ductal tree is retained. Intriguingly, the remaining duct progenitors do not compensate for loss of Sox10 and lack plasticity to properly form secretory units. However, overexpression of Sox10 in these ductal progenitors enhances their plasticity toward KIT+ progenitors and induces differentiation into secretory units. Therefore, Sox10 controls plasticity and multi-potency of epithelial KIT+ cells in secretory organs, such as mammary, lacrimal, and salivary glands. : In this manuscript, Lombaert and colleagues discovered that transcription factor Sox10 is not only essential to maintain epithelial progenitors in exocrine glands, but also acts as a master regulator to induce plasticity toward secretory units. These results provide new avenues for directed differentiation and engineering of secretory units in vitro and/or in vivo. Keywords: SOX10, secretory unit, cell fate, stem/progenitor cell, exocrine glands, salivary gland, mammary gland, lacrimal gland, KIT

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