Delineating nuclear reprogramming

Nuclear reprogramming is described as a molecular switch,triggered by the conversion of one cell type to another.Several key experiments in the past century have provided insight into the field of nuclear repro-gramming.Previously deemed impossible,this re-search area is now brimming with new findings and developments.In this review,we aim to give a historical perspective on how the notion of nuclear reprogram-ming was established,describing main experiments that were performed,including(1)somatic cell nuclear transfer,(2)exposure to cell extracts and cell fusion,and(3)transcription factor induced lineage switch.Ultimately,we focus on(4)transcription factor induced pluripotency,as initiated by a landmark discovery in 2006,where the process of converting somatic cells to a pluripotent state was narrowed down to four tran-scription factors.The conception that somatic cells possess the capacity to revert to an immature status brings about huge clinical implications including per-sonalized therapy,drug screening and disease model-ing.Although this technology has potential to revolu-tionize the medical field,it is still impeded by technical and biological obstacles.This review describes the effervescent changes in this field,addresses bottle-necks hindering its advancement and in conclusion,applies the latest findings to overcome these issues.

Oocyte-associated transcription factors in reprogramming after somatic cell nuclear transfer:a review

Oocytes are unique cells with the inherent capability to reprogram nuclei.The reprogramming of the somatic nucleus from its original cellular state to a totipotent state is essential for term development after somatic cell nuclear transfer.The nuclear-associated factors contained within oocytes are critical for normal fertilization by sperm or for somatic cell nuclear reprogramming.The chromatin of somatic nuclei can be reprogrammed by factors in the egg cytoplasm whose natural function is to reprogram sperm chromatin.The oocyte first obtains its reprogramming capability in the early fetal follicle,and then its capacity is enriched in the late growth phase and reaches its highest capability for reprogramming as fully-grown germinal vesicle oocytes.The cytoplasmic milieu most likely contains all of the specific transcription and/or reprogramming factors necessary for cellular reprogramming.Certain transcription factors in the cytoplast may be critical as has been demonstrated for induced pluripotent stem cells.The maternal pronucleus exerts a predominant,transcriptiondependent effect on embryo cytofragmentation,with a lesser effect imposed by the ooplasm and the paternal pronucleus.With deep analysis of transcriptomics in oocytes and early developmental stage embryos more maternal transcription factors inducing cellular reprogramming will be identified.

Overexpression of Stella improves the efficiency of nuclear transfer reprogramming

In mammalians, the state of a somatic cell can be reversed from the terminal state to the totipotent state by means of somatic cell nuclear transfer （SCNT） （Gurdon, 1962） or induced pluripotent stem cells （iPSCs） （Takahashi and Yamanaka, 2006）. The DNA methylation and transcriptome profiles of embryonic stern cells （ESCs） derived from SCNT embryos （NT-ESCs） correspond closely to those of ESCs derived from in vitro fertilization embryos （IVF- ESCs）. In contrast, iPSCs differ from both NT-ESCs and IVF-ESCs in that they retain the residual DNA methylation patterns of their parental somatic cells. As SCNT can be used to faithfully reprogram human somatic cells to pluripotency, it is ideal for cell replacement therapies （Ma et al., 2014）. Following the successful production of the first human NT-ESCs （Tachibana et al., 2013） and the later gen- eration of human NT-ESCs based on cells from elderly adults or pa- tient cells （Chung et al., 2014; Yamada et al., 2014）, a version of the SCNT technique for human therapeutics comes closer to reality. However, no matter what animal species or donor cell types are used in the cloned process, the cloning efficiency remains undesir- able. Besides, there are many phenotypic abnormalities in cloned animals, containing frequent embryonic and perinatal death and placentomegaly, and the underlying mechanisms remain unclear （Yang et al, 2007）.