A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells
Changes in ASE reflects X-chromosomal silencing during iPS reprogramming.
(A) In the two iPS clones derived from PGP9, the X-chromosomal ASE ratio was highly reproducible, in which 7 out of 14 SNPs escaped complete silencing (R2 = 0.9833). (B) When compared to their parental primary fibroblasts (clonally derived PGP9Bx1F1), we observed that the X-chromosomal ASE ratio was now inversely proportional (R2 = 0.5199), strongly suggesting the re-activation of the random silencing mechanism. (C) Autosomal genes in the same pair showed a positive correlation (R2 = 0.6343). (D) When PGP9Bx1F1 (clonally derived) was compared to PGP9Bx2F1 (non-clonal), the X-chromosomal ASE ratio confirmed the clonality of PGP9Bx1F1 used for iPS reprogramming.