Ascorbic acid improves pluripotency of human parthenogenetic embryonic stem cells through modifying imprinted gene expression in the Dlk1-Dio3 region

Abstract

IntroductionHuman parthenogenetic embryonic stem cells (hpESCs) are generated from artificially activated oocytes, however, the issue of whether hpESCs have equivalent differentiation ability to human fertilized embryonic stem cells remains controversial.MethodshpESCs were injected into male severe combined immunodeficiency (SCID) mice and the efficiency of teratoma formation was calculated. Then the gene expression and methylation modification were detected by real time-PCR and bisulfate methods.ResultsComparison of five hpESCs with different differentiation abilities revealed that levels of paternal genes in the Dlk1-Dio3 region on chromosome 14 in the hpESCs with high differentiation potential are enhanced, but strictly methylated and silenced in the hpESCs with lower differentiation potential. Treatment with ascorbic acid, rescued their ability to support teratoma formation and altered the expression profiles of paternally expressed genes in hpESCs that could not form teratoma easily. No differences in the expression of other imprinting genes were evident between hpESCs with higher and lower differentiation potential, except for those in the Dlk1-Dio3 region.ConclusionsThe Dlk1-Dio3 imprinting gene cluster distinguishes the differentiation ability of hpESCs. Moreover, modification by ascorbic acid may facilitate application of hpESCs to clinical settings in the future by enhancing their pluripotency.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0054-9) contains supplementary material, which is available to authorized users.

Oocyte collection and in vitro maturation after train transportation of human follicular fluid aspirated from resected non‐stimulated ovaries of patients with endometrial adenocarcinoma

“…In this study, an average of 8.1 ± 8.4 oocytes per patient and a maturation rate of 38.6% were obtained following HFF transportation. In FP, even one mature oocyte is valuable, and in research setting, human oocytes are needed in many situations, for example, when creating parthenogenetic embryonic stem cells . In order to reduce the adverse effects on oocytes, research on improving HFF transportation method is needed in the future.…”

“…33 Another limitation is that the study design did not involve as- 34,35 and in research setting, human oocytes are needed in many situations, for example, when creating parthenogenetic embryonic stem cells. 40 In order to reduce the adverse effects on oocytes, research on improving HFF transportation method is needed in the future.…”

The Type 3 Deiodinase: Epigenetic Control of Brain Thyroid Hormone Action and Neurological Function

“…Few factors have been identified to alter Dio3 allelic expression. Ascorbic acid has been found to prevent loss of imprinting at the Dlk1 - Dio3 domain in stem cells [ 116 , 117 ], and maternal immune response or cannabinoid exposure in adolescence alters the imprinting of Dlk1 - Dio3 in the entorhinal cortex, a region implicated in schizophrenia [ 118 ].…”

Erratum to: Ascorbic acid improves pluripotency of human parthenogenetic embryonic stem cells through modifying imprinted gene expression in the Dlk1-Dio3 region

“…Following the publication of our article [ 1 ], we noticed that some incorrect images had been incorporated into figure twoB (included here as Fig. 1b ) and threeF-H (included here as Fig.…”