High prevalence of evolutionarily conserved and species-specific genomic aberrations in mouse pluripotent stem cells.
Mouse pluripotent stem cells (PSCs) are the best studied pluripotent system and are regarded as the "gold standard" to which human PSCs are compared. However, while the genomic integrity of human PSCs has recently drawn much attention, mouse PSCs have not been systematically evaluated in this regard. The genomic stability of PSCs is a matter of profound significance, as it affects their pluripotency, differentiation, and tumorigenicity. We thus performed a thorough analysis of the genomic integrity of 325 samples of mouse PSCs, including 127 induced pluripotent stem cell (iPSC) samples. We found that genomic aberrations occur frequently in mouse embryonic stem cells of various mouse strains, add in mouse iPSCs of various cell origins and derivation techniques. Four hotspots of chromosomal aberrations were detected: full trisomy 11 (with a minimally recurrent gain in 11qE2), full trisomy 8, and deletions in chromosomes 10qB and 14qC-14qE. The most recurrent aberration in mouse PSCs, gain 11qE2, turned out to be fully syntenic to the common aberration 17q25 in human PSCs, while other recurrent aberrations were found to be species specific. Analysis of chromosomal aberrations in 74 samples of rhesus macaque PSCs revealed a gain in chromosome 16q, syntenic to the hotspot in human 17q. Importantly, these common aberrations jeopardize the interpretation of published comparisons of PSCs, which were unintentionally conducted between normal and aberrant cells. Therefore, this work emphasizes the need to carefully monitor genomic integrity of PSCs from all species, for their proper use in biomedical research.
Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
Uri
U
Ben-David
Nissim
N
Benvenisty
D000818:Animals; D002869:Chromosome Aberrations; D017124:Conserved Sequence / Q000235:genetics*; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics*; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics; D051379:Mice; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D013045:Species Specificity; D026801:Synteny / Q000235:genetics