Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

The International Stem Cell Initiative analyzed 127 human embryonic stem cell lines and 11 induced pluripotent cell lines, from 39 laboratories worldwide for genetic changes occurring during culture. Most cell lines were analyzed at an early and late passage. Population structure analysis from SNP detection revealed that the cell lines included representatives of all major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed but haphazardly with no link to time in culture. Structural variants (SVs), below the level of standard chromosome banding, determined from the SNP arrays, also appeared sporadically but no common variants related to culture were observed on chromosomes 1, 12 and 17. However, overlapping SV gains acquired in the chromosome 20q11.21 region during extended culture were identified in over 20% of the cell lines. Three genes within the minimal shared region, ID1, BCL2L1, and HM13, are expressed in human ES cells, with BCL2L1 a strong candidate for driving this culture adaptation of ES cells.