Expression of 'Blimp1' gene leads to the discovery of cells responsible for skin's sebaceous gland

The research focuses on the skin’s sebaceous gland, which is linked to the hair shaft and secretes an oily mixture called sebum. But until today how the sebaceous gland is formed during development was a matter of debate: one group of scientists proposed that skin stem cells produce the gland and a second group suggested that it had its own progenitor cells. In new research, published in the August 11 issue of Cell, Elaine Fuchs, a Howard Hughes Medical Institute investigator at Rockefeller University, settles this argument, showing that at the site where the sebaceous gland adjoins the hair follicle, a unique population of cells exists whose sole job is to make, and maintain, the sebaceous gland.

“We were exploring the expression of a transcription factor called Blimp1, which had surfaced in a genetic screen that we had conducted.” explains Fuchs, who is the Rebecca C. Lancefield Professor and head of the Laboratory of Mammalian Cell Biology and Development at Rockefeller. “We were surprised to find that Blimp1 was expressed in a small population of cells within the sebaceous gland. We knew these cells were skin keratinocytes but no one had ever described their existence and therefore, we had no clues about their relationship to the gland.”

Valerie Horsley, a postdoc in the Fuchs lab and first author of the paper, had been interested in Blimp1’s role in hair follicle development, and had engineered mice that were missing the Blimp1 gene in their skin. “When the mice were born, they formed normal hair follicles, which was quite disappointing,” says Horsley. “But when they were around one month of age I noticed that the mice started getting very oily skin.”

The sebaceous glands in mice missing Blimp1 were much larger than in normal skin. This happens in another genetically altered mouse, one overexpessing the c-myc gene, which has been implicated in many different kinds of cancers. Horsley found that Blimp1 usually acts to repress c-myc expression, and in mice without Blimp1 c-myc expression was increased, causing the sebaceous gland to contain cells that divide more frequently. When Horsley tagged the Blimp1 positive cells and tracked them, she found that the daughters of the Blimp1 cells contribute to the entire gland. Also, when grown outside in culture, the cells that make Blimp1 can divide and self-renew, as well as make the cell types important for generating the oils of the sebaceous gland.

“The data show clearly that these cells are the progenitors for the entire sebaceous gland,” says Horsley. “And Blimp1 is somehow controlling this progenitor population, regulating how many cells are allowed into the gland. This is the first molecular characterization of these cells.”

“This study has implications for understanding sebaceous gland disorders ranging from acne to sebaceous cell cancers,” says Fuchs. “And it not only gives us a handle on these novel resident stem cells, but also clues to how stem cells can control the balance of proliferation and differentiation in tissues.”