Abnormalities in human pluripotent cells due to reprogramming mechanisms

Functional Human Oocytes Generated by Transfer of Polar Body Genomes

“…This process undergoes dynamic changes during and after fertilization reflecting developmental reprogramming (Canovas and Ross, 2016). Also, the establishment of stable ESCs is associated with major changes in methylation profiles as the genome reconfigures to the pluripotent state (Lister et al, 2009;Lister et al, 2011;Ma et al, 2014). To evaluate the normalcy of these changes, we conducted genome-wide DNA methylation analysis of PBNT1 and hESO-14 cell lines using high-coverage, base-resolution MethylCseq (Lister et al, 2009) Both lines showed similar levels of CG methylation, a difference of only 0.7% between PBNT1 (86.1%) and hESO-14 (85.4%), and non-CG methylation, a difference of only 0.4% between PBNT1 (1.3%) and hESO-14 (0.9%) ( Figure 3A and 3B).…”

“…To evaluate the normalcy of these changes, we conducted genome-wide DNA methylation analysis of PBNT1 and hESO-14 cell lines using high-coverage, base-resolution MethylCseq (Lister et al, 2009) Both lines showed similar levels of CG methylation, a difference of only 0.7% between PBNT1 (86.1%) and hESO-14 (85.4%), and non-CG methylation, a difference of only 0.4% between PBNT1 (1.3%) and hESO-14 (0.9%) ( Figure 3A and 3B). Pairwise comparison of these two samples identified only 116 CG differentially methylated regions (DMRs) (Bellieni, 2012) and 4 non-CG mega DMRs spanning about 500kb (He and Ecker, 2015;Lister et al, 2009;Ma et al, 2014) (Figure 3C; Table S5, FDR < 0.01). Visual inspection implies the conformation of these DMRs ( Figure 3D and 3E), but there was no enrichment in gene ontology (GO) terms, genetic features ( Figure 3C), or correlation to the transcriptional profile.…”

Generation of fertile offspring from Kitw/Kitwv mice through differentiation of gene corrected nuclear transfer embryonic stem cells

“…However, the concern that iPSCs and their derivatives may transform to tumor cells may hinder the clinical application of iPSCs [25]. Recently, both human and mouse SCNT ESCs were reported to more closely resemble the relative ESCs [26,27]. In addition, cells may also accumulate mutations at both genetic and epigenetic levels when subjected to gene correction and long-time in vitro culture.…”

Present and future challenges of induced pluripotent stem cells

“…Ma et al concluded that iPSCs have inherent abnormalities, because the similarity of SCNTESCs to ESCs derived from in vitro fertilized eggs is greater than that of iPSCs [82]. They found that iPSCs have aberrant DNA methylation statuses for some imprinted genes, such as DIRAS3, MEG3 and PEG3, and regions of X-chromosome inactivation.…”

“…Recently, the invention of human somatic cell nuclear transfer (SCNT)-ESCs has been reported [78][79][80], and the comparison of gene expressions, epigenetic statuses and genetic alterations between isogenic human SCNT-ESCs and iPSCs derived from the same somatic cell cultures has been discussed [81,82]. Ma et al concluded that iPSCs have inherent abnormalities, because the similarity of SCNTESCs to ESCs derived from in vitro fertilized eggs is greater than that of iPSCs [82].…”