TRANSCRIPTOMIC AND EPIGENOMIC CHARACTERISATION OF BALDING AND NON-BALDING HUMAN DERMAL PAPILLA CELLS

Abstract

ANDROGENETIC ALOPECIA (AGA) IS A COMMON HERITABLE AND ANDROGEN-DEPENDENT HAIR LOSS CONDITION IN MEN, WHICH CAUSATIVE GENES ARE CURRENTLY UNCLEAR. IMMORTALISED HUMAN DERMAL PAPILLA CELL (DPC) LINES FROM BALDING (BAB) AND NON-BALDING (BAN) SCALP WAS SHOWN TO RETAIN HIGH PROPORTIONS OF DP SIGNATURE AND THUS ARE SUITABLE MODELS IN AGA/HAIR-RELATED STUDIES. <I>AR</I> BUT NOT <I>EDA2R</I> WAS IDENTIFIED AS THE CANDIDATE GENE AT THE MAJOR XQ12 AGA RISK LOCUS, WITH RS2207081 BEING THE LIKELY FUNCTIONAL SNP. THE DOWN-REGULATION OF VASCULATURE-RELATED GENES IN BAB COMPARED TO BAN SUGGEST THAT DEFICIENCY OF DPC FROM BALDING SCALPS IN FOSTERING VASCULARISATION AROUND THE HAIR FOLLICLE MAY CONTRIBUTE TO AGA DEVELOPMENT. IN AN IMPROVED 3D CO-CULTURING PROTOCOL WITH EPIDERMAL KERATINOCYTES, MITOCHONDRIA-RELATED GENES WERE OBSERVED TO BE UP-REGULATED IN BAB AGGREGATES AS COMPARED TO BAN AGGREGATES, SUGGESTING POTENTIAL DEFECTS IN MITOCHONDRIAL RESPIRATORY CAPACITY IN BAB THAT CONTRIBUTE TO THE BALDING