RNA-seq analysis of Lgr6⁺ stem cells and identification of an Lgr6 isoform

We studied Lgr6⁺ stem cells in experimental UV carcinogenesis in hairless mice. For further characterization through RNA-seq, these stem cells were isolated by FACS from transgenic hairless mice bearing an EGFP-Ires-CreERT2 reporter cassette inserted into exon 1 of the Lgr6 gene (purity confirmed by human ERT2 expression). Between Lgr6/EGFP⁺ and Lgr6/EGFP^- basal cells (Tg/wt), 682 RNAs were differentially expressed, indicating stemness and expression of cancer-related pathways in Lgr6/EGFP⁺ cells. We discovered that suspected "Lgr6 null" mice (Tg/Tg) expressed RNA of an Lgr6 isoform (delta-Lgr6, lacking 74 N-terminal aa) which could be functional and explain the lack of a phenotype.