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SignificanceWe show that mutations in HMGA2 affect fetal resource allocation, testis descent, and the size of pigs and provides a target for gene modification that can be used to modulate size in other mammalian species. This can have implications in agriculture as well as in the development of new strains of companion animals. In addition, most xenograft pig donors have adult organs larger than those of humans. Recently, it has been shown that regulation of organ growth is donor-controlled, not host-controlled, resulting in organ overgrowth and damage after transplantation. We show here that the HMGA2 gene is a potential target for organ-size regulation in xenotransplantation.

Hair follicle stem cells are key for driving growth and homeostasis of the hair follicle niche, have remarkable regenerative capacity throughout hair cycling, and display fate plasticity during cutaneous wound healing. Due to the need for a transgenic reporter, essentially all observations related to LGR5-expressing hair follicle stem cells have been generated using transgenic mice, which have significant differences in anatomy and physiology from the human. Using a transgenic pig model, a widely accepted model for human skin and human skin repair, we demonstrate that LGR5 is a marker of hair follicle stem cells across species in homeostasis and development. We also report the strong similarities and important differences in expression patterns, gene expression profiles, and developmental processes between species. This information is important for understanding the fundamental differences and similarities across species, and ultimately improving human hair follicle regeneration, cutaneous wound healing, and skin cancer treatment.

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