title: Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells.
abstract: Human pluripotent stem cells, including cloned embryonic and induced pluripotent stem cells, offer a limitless cellular source for regenerative medicine. However, their derivation efficiency is limited, and a large proportion of cells are arrested during reprogramming. In the current study, we explored chromosome microdeletion/duplication in arrested and established reprogrammed cells. Our results show that aneuploidy induced by somatic cell nuclear transfer technology is a key factor in the developmental failure of cloned human embryos and primary colonies from implanted cloned blastocysts and that expression patterns of apoptosis-related genes are dynamically altered. Overall, ~20%-53% of arrested primary colonies in induced plurpotent stem cells displayed aneuploidy, and upregulation of P53 and Bax occurred in all arrested primary colonies. Interestingly, when somatic cells with pre-existing chromosomal mutations were used as donor cells, no cloned blastocysts were obtained, and additional chromosomal mutations were detected in the resulting iPS cells following long-term culture, which was not observed in the two iPS cell lines with normal karyotypes. In conclusion, aneuploidy induced by the reprogramming process restricts the derivation of pluripotent stem cells, and, more importantly, pre-existing chromosomal mutations enhance the risk of genome instability, which limits the clinical utility of these cells.
authors.affiliation: 1] Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China [3] Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chang
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Hongcui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: 1] Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China [3] Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
authors.affiliation: 1] Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, 100191, China [3] Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D019976:Cloning, Organism; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D042822:Genomic Instability; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053652:Nuclear Transfer Techniques