Epigenetic Aberrations Are Not Specific to Transcription Factor-Mediated Reprogramming

Tiemann, Ulf; Wu, Guangming; Marthaler, Adele G.; Schöler, Hans R.; Tàpia, Natalia

doi:10.1016/j.stemcr.2015.11.007

Cited by 8 publications

(7 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, imprinting errors are observed in iPSCs, suggesting that these epigenetic anomalies are related to the reprogramming process and could be directly responsible for the variable phenotypes and low success rates of both cloning and iPS derivation procedures [ 139 ]. Certainly, the epigenetic abnormalities detected in iPSCs are not specific to transcription factor-mediated reprogramming [ 140 ]. It is difficult to program via SCNT and iPSC induction, and it is also a challenge to cause two sperm from paternal genomes to construct a DSC embryo with the correct reprogramming procedure.…”

Section: Challenges Of Dsc Scnt and Ipscsmentioning

confidence: 99%

Double sperm cloning (DSC) is a promising strategy in mammalian genetic engineering and stem cell research

Zhang

Huang

et al. 2020

Stem Cell Res Ther

View full text Add to dashboard Cite

Embryonic stem cells (ESCs) derived from somatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) are promising tools for meeting the personalized requirements of regenerative medicine. However, some obstacles need to be overcome before clinical trials can be undertaken. First, donor cells vary, and the reprogramming procedures are diverse, so standardization is a great obstacle regarding SCNT and iPSCs. Second, somatic cells derived from a patient may carry mitochondrial DNA mutations and exhibit telomere instability with aging or disease, and SCNT-ESCs and iPSCs retain the epigenetic memory or epigenetic modification errors. Third, reprogramming efficiency has remained low. Therefore, in addition to improving their success rate, other alternatives for producing ESCs should be explored. Producing androgenetic diploid embryos could be an outstanding strategy; androgenic diploid embryos are produced through double sperm cloning (DSC), in which two capacitated sperms (XY or XX, sorted by flow cytometer) are injected into a denucleated oocyte by intracytoplasmic sperm injection (ICSI) to reconstruct embryo and derive DSC-ESCs. This process could avoid some potential issues, such as mitochondrial interference, telomere shortening, and somatic epigenetic memory, all of which accompany somatic donor cells. Oocytes are naturally activated by sperm, which is unlike the artificial activation that occurs in SCNT. The procedure is simple and practical and can be easily standardized. In addition, DSC-ESCs can overcome ethical concerns and resolve immunological response matching with sperm providers. Certainly, some challenges must be faced regarding imprinted genes, epigenetics, X chromosome inactivation, and dosage compensation. In mice, DSC-ESCs have been produced and have shown excellent differentiation ability. Therefore, the many advantages of DSC make the study of this process worthwhile for regenerative medicine and animal breeding.

show abstract

Section: Challenges Of Dsc Scnt and Ipscsmentioning

confidence: 99%

Double sperm cloning (DSC) is a promising strategy in mammalian genetic engineering and stem cell research

Zhang

Huang

et al. 2020

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…This concept stems from a number of works that investigated the differences in differentiation capacity of hiPSC and described them to epigenetic marks inherited from the cells of origin and that had not been correctly reset during the reprogramming process (Bar-Nur et al 2011, Ohi et al 2011). However, current knowledge suggests that the reprogramming process itself is prone to inducing epigenetic abnormalities (Tiemann et al 2016) and that the main factor influencing the differentiation propensity is not an epigenetic memory as such, but the (epi)-genetic background of the donor of the source cells (reviewed in Keller et al 2018).…”

Section: Suboptimal Differentiationmentioning

confidence: 99%

Human pluripotent stem cells in regenerative medicine: where do we stand?

2018

View full text Add to dashboard Cite

Human pluripotent stem cells have the capacity to self-renew indefinitely and the ability to differentiate into all cell types of a human body. These characteristics instill them with an enormous promise in regenerative medicine, where they could be used in cell, tissue and even organ-based replacement therapy. In this review, we discuss their potential clinical applications and the advantages and pitfalls for the different types of human pluripotent stem cells to transition from the bench to the bedside. We provide an overview of the current clinical trials, and the specific challenges we are still facing, including immune compatibility, suboptimal differentiation, risk of tumor formation and genome instability.

show abstract

“…However, a comparison between lentiviral encoded transcription factor‐mediated reprogramming of germline stem cells (GSC) to iPSCs, to culture condition‐mediated reprogramming of the same GSC lines, demonstrated that the two methods were similar in both the retention of epigenetic marks characteristic of GSC and the incidence of epigenetic errors attributable to the reprogramming process. Thus, alternative reprogramming methods may not be superior to standard lentivirus‐based reprogramming in terms of epigenetic memory and induction of epigenetic errors .…”

Section: Induced Pluripotent Cellsmentioning

confidence: 99%

Concise Review: Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer: A Horse in the Race?

et al. 2016

View full text Add to dashboard Cite

Embryonic stem cells (ESC) hold promise for the treatment of human medical conditions but are allogeneic. Here, we consider the differences between autologous pluripotent stem cells produced by nuclear transfer (NT-ESCs) and transcription factor-mediated, induced pluripotent stem cells (iPSCs) that impact the desirability of each of these cell types for clinical use. The derivation of NT-ESCs is more cumbersome and requires donor oocytes; however, the use of oocyte cytoplasm as the source of reprogramming factors is linked to a key advantage of NTESCs-the ability to replace mutant mitochondrial DNA in a patient cell (due to either age or inherited disease) with healthy donor mitochondria from an oocyte. Moreover, in epigenomic and transcriptomic comparisons between isogenic iPSCs and NT-ESCs, the latter produced cells that more closely resemble bona fide ESCs derived from fertilized embryos. Thus, although NTESCs are more difficult to generate than iPSCs, the ability of somatic cell nuclear transfer to replace aged or diseased mitochondria and the closer epigenomic and transcriptomic similarity between NT-ESCs and bona fide ESCs may make NT-ESCs superior for future applications in regenerative medicine. STEM CELLS 2017;35:26-34 SIGNIFICANCE STATEMENTThis review describes recently developed human ESCs from somatic cell nuclear transfer blastocysts and discusses their advantages and limitations compared to other types of human pluripotent stem cells.

show abstract

Epigenetic Aberrations Are Not Specific to Transcription Factor-Mediated Reprogramming

Cited by 8 publications

References 22 publications

Double sperm cloning (DSC) is a promising strategy in mammalian genetic engineering and stem cell research

Double sperm cloning (DSC) is a promising strategy in mammalian genetic engineering and stem cell research

Human pluripotent stem cells in regenerative medicine: where do we stand?

Concise Review: Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer: A Horse in the Race?

Contact Info

Product

Resources

About