Relative to fESC, hypermethylated DMRs predominated in NP-iPSC and Bl-iPSC (417 (75%) and 1423 (96%), respectively; Supplementary Table 1b), confirming that even when pluripotency is documented by stringent criteria, iPSC retain residual methylation. By analysis of overlapping DMRs, Bl-iPSC cluster with progenitors of the lymphoid lineage (CLP) rather than the myeloid lineage (Supplementary Fig. 4a; Supplementary Table 425). To illustrate this point, the Gcnt2 gene, which encodes the enzyme responsible for the blood group I antigen, and Gata2, a regulator of hematopoiesis and erythropoiesis, are both hypermethylated and transcriptionally silent in the lymphoid lineage25. Bl-iPSC showed hypermethylation at these loci relative to fESC, whereas the myeloid-derived B-iPSC did not (Supplementary Fig. 11). Thus, a methylation signature correctly identifies the blood lineage of origin of B-lymphocyte derived iPSC.
