TY - JOUR
T1 - Genomic Analysis of hESC Pedigrees Identifies De Novo Mutations and Enables Determination of the Timing and Origin of Mutational Events
AU - Ben-Yosef, Dalit
AU - Boscolo, Francesca S.
AU - Amir, Hadar
AU - Malcov, Mira
AU - Amit, Ami
AU - Laurent, Louise C.
N1 - Funding Information:
The laboratory of Susan Fisher (UCSF, including Tamara Zdravkovic and Olga Genbacev) made the blastomere-derived lines available to the authors. The derivation and characterization of these lines were supported by grants from the California Institute for Regenerative Medicine (RL1-00648 and RC1-00113). We thank Jeanne F. Loring and Candace Lynch for running the genomic DNA from the hESC cultures on SNP genotyping microarrays, supported by CIRM TR-1250. We thank Dr. Sagit Peleg and Veronica Gold for performing the PGD analysis of patients and the haplotype analysis for the PGD-HESC lines, Tsvia Frumkin for the karyotype analysis and skillful assistance in the stem cell research lab, and the embryologists of the Racine IVF lab (Ariela Carmon, Tanya Cohen, Tamar Shwartz, and Nava Mei-Raz) for their skillful assistance. We thank Sigalit Siso from Tel Aviv Medical Center for the graphics. This research was partly funded by a grant from the Recanaty Foundation, Tel Aviv University. F.S.B. was supported by a California Institute for Regenerative Medicine (CIRM) Bridges grant to the California State University, Channel Islands. F.S.B. and L.C.L. were supported by The Hartwell Foundation. L.C.L. was supported by NIH K12 HD001259.
PY - 2013/9/26
Y1 - 2013/9/26
N2 - Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs) is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs) have shown that deletions and regions of loss of heterozygosity (LOH) tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs), we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs
AB - Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs) is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs) have shown that deletions and regions of loss of heterozygosity (LOH) tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs), we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs
UR - http://www.scopus.com/inward/record.url?scp=84884593771&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2013.08.009
DO - 10.1016/j.celrep.2013.08.009
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AN - SCOPUS:84884593771
SN - 2211-1247
VL - 4
SP - 1288
EP - 1302
JO - Cell Reports
JF - Cell Reports
IS - 6
ER -
