SummaryUnderstanding 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.
The Granzyme (Gzm) family has classically been recognized as a cytotoxic tool utilized by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells to illicit cell death to infected and cancerous cells. Their importance is established based on evidence showing that deficiencies in these cell death executors result in defective immune responses. Recent findings have shown the importance of Granzyme B (GzmB) in regulatory immune cells, which may contribute to tumor growth and immune evasion during cancer development. Other studies have shown that members of the Gzm family are important for biological processes such as extracellular matrix remodeling, angiogenesis and organized vascular degradation. With this growing body of evidence, it is becoming more important to understand the broader function of Gzm’s rather than a specific executor of cell death, and we should be aware of the many alternative roles that Gzm’s play in physiological and pathological conditions. Therefore, we review the classical as well as novel non-canonical functions of GzmB and discuss approaches to utilize these new findings to address current gaps in our understanding of the immune system and tissue development.
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