Epigenomic profiling of hair follicle stem cells identifies PRDM16 as a regulator of sebaceous gland homeostasis [ChIP-seq]

The epidermis consists of different compartments such as the hair follicle (HF), sebaceous gland (SG) and interfollicular epidermis (IFE), each containing distinct stem cell (SC) populations. However, with the exception of the SCs residing within the HF bulge, other epidermal SC populations remain poorly characterized at the molecular level. Here we used an epigenomic strategy that combines H3K27me3 ChIP-seq and RNA-seq profiling to identify major regulators of HFSC located outside the bulge. When applied to the bulk of HFSC isolated from mouse skin our approach identified both previously known and potentially novel non-bulge HFSC regulators. Among the latter, we found that PRDM16 was preferentially expressed within the Junctional Zone (JZ). To investigate PRDM16 function within the JZ SCs, we generated an epidermal-specific Prdm16 Knock-out mouse model (K14-Cre-Prdm16fl/fl). Notably, although these K14-Cre-Prdm16fl/fl mice did not show any major skin or hair abnormalities, the homeostasis of the SG was clearly compromised. Namely, PRDM16 deficient mice displayed enlarged SGs and excessive sebum production, thus resembling some of the features associated with certain human conditions (i.e. acne, sebaceous hyperplasia). Overall, our study provides a list of putative novel regulators of HFSC outside the bulge and identifies PRDM16 as a major regulator of SG homeostasis. Genome-wide binding profiles for H3K27me3 and H3K4me3 were generated in Αlpha6+/Sca1- cells isolated from back skin of P56 mice using ChIP-seq.