Pluripotency of induced pluripotent stem cells

Recent studies have demonstrated that differentiated somatic cells from various mammalian species can be reprogrammed into induced pluripotent stem （iPS） cells by the ectopic expression of four transcription factors that are highly expressed in embryonic stem （ES） cells. The generation of patient-specific iPS cells directly from somatic cells without using oocytes or embryos holds great promise for curing numerous diseases that are currently unresponsive to traditional clinical approaches. However, some recent studies have argued that various iPS cell lines may still retain certain epigenetic memories that are inherited from the somatic cells. Such observations have raised concerns regarding the safety and efficacy of using iPS cell derivatives for clinical applications. Recently, our study demonstrated full pluripotency of mouse iPS cells by tetraploid complementation, indicating that it is possible to obtain fully reprogrammed iPS cells directly from differentiated somatic cells. Therefore, we propose in this review that further comprehensive studies of both mouse and human iPS cells are required so that additional information will be available for evaluating the quality of human iPS cells.

The chemical reprogramming of unipotent adult germ cells towards authentic pluripotency and de novo establishment of imprinting

Although somatic cells can be reprogrammed to pluripotent stem cells(PsCs)with pure chemicals,authentic pluripotency of chemically induced pluripotent stem celis(CipsCs)has never been achieved through tetraploid complementation assay.Spontaneous reprogramming of spermatogonial stem cells(ssCs)was another non-transgenic way to obtain PsCs,but this process lacks mechanistic explanation.Here,we reconstructed the trajectory of mouse SsC reprogramming and developed a five-chemical combination,boosting the reprogramming effciency by nearly 80-to 100-folds.More importantly,chemical induced germline-derived PsCs(5C-gPSCs),but not gpsCs and chemical induced pluripotent stem cells,had authentic pluripotency,as determined by tetraploid complementation.Mechanistically,ssCs traversed through an inverted pathway of in vivo germ ceil development,exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts.Besides,ssC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5c-gPsCs,which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles.Our work sheds ight on the unique regulatory network underpinning SsC reprogramming,providing insights to understand generic mechanisms for cell-fate decision and epigenetic-relateddisorders in regenerative medicine.