Cell reprogramming is a progress in which the memory of a mature cell is erased and then the cell develops novel phenotype and function; ultimately, the fate of the cell changes. Cell reprogramming usually occurs at genes expression levels that no genomic DNA sequence change will be involved. By changing the programs of the genetic expressions of cells in terms of space and time, cell reprogramming alters the differentiation of cells and thus produces the required cells. Further research on cells reprogramming will elucidate the mechanisms that govern the cell development, and thus provides more information of the sources of seed cells used for regeneration medicine. More cells differentiated from many terminally differentiated cells will be obtained, which is extremely important for the understanding of molecular differentiation and for the development of cell replacement therapy. This article summarizes the classification, influencing factors, approaches and latest advances of cells reprogramming.
Animals ; Cell Dedifferentiation ; genetics ; Cell Differentiation ; genetics ; Cellular Reprogramming ; Gene Expression ; Humans ; Nuclear Transfer Techniques

The success of yielding induced pluripotent stem (iPS) cells from human somatic cells demonstrates the important role of reprogramming in the formation of stem/progenitor cells and initiates the exploration of the origin of leukemia stem cells. In our previous work, we have found two types of leukemia, bona fide leukemia and non-bona fide leukemia. Different leukemias originate from different leukemia stem/progenitor cells which are critical to the genesis and evolution of leukemia. Bona fide leukemia and non-bona fide leukemia originate from leukemia stem cells and progenitor cells, respectively. Recent research suggests that different types of leukemia are influenced by the reprogramming state of their origin cells.
Cell Differentiation ; Cellular Reprogramming ; Humans ; Induced Pluripotent Stem Cells ; Leukemia ; genetics ; Neoplastic Stem Cells ; Stem Cells

The somatic epigenome can be reprogrammed to a pluripotent state by a combination of transcription factors. Altering cell fate involves transcription factors cooperation, epigenetic reconfiguration, such as DNA methylation and histone modification, posttranscriptional regulation by microRNAs, and so on. Nevertheless, such reprogramming is inefficient. Evidence suggests that during the early stage of reprogramming, the process is stochastic, but by the late stage, it is deterministic. In addition to conventional reprogramming methods, dozens of small molecules have been identified that can functionally replace reprogramming factors and significantly improve induced pluripotent stem cell (iPSC) reprogramming. Indeed, iPS cells have been created recently using chemical compounds only. iPSCs are thought to display subtle genetic and epigenetic variability; this variability is not random, but occurs at hotspots across the genome. Here we discuss the progress and current perspectives in the field. Research into the reprogramming process today will pave the way for great advances in regenerative medicine in the future.
Animals ; Cell Differentiation ; Cellular Reprogramming ; MicroRNAs ; genetics ; Models, Biological ; Pluripotent Stem Cells ; cytology ; metabolism ; Stochastic Processes

Cell fate conversion is considered as the changing of one type of cells to another type including somatic cell reprogramming (de-differentiation), differentiation, and trans-differentiation. Epithelial and mesenchymal cells are two major types of cells and the transitions between these two cell states as epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) have been observed during multiple cell fate conversions including embryonic development, tumor progression and somatic cell reprogramming. In addition, MET and sequential EMT-MET during the generation of induced pluripotent stem cells (iPSC) from fibroblasts have been reported recently. Such observation is consistent with multiple rounds of sequential EMT-MET during embryonic development which could be considered as a reversed process of reprogramming at least partially. Therefore in current review, we briefly discussed the potential roles played by EMT, MET, or even sequential EMT-MET during different kinds of cell fate conversions. We also provided some preliminary hypotheses on the mechanisms that connect cell state transitions and cell fate conversions based on results collected from cell cycle, epigenetic regulation, and stemness acquisition.
Animals ; Cell Differentiation ; Cell Lineage ; Cellular Reprogramming ; Epigenesis, Genetic ; genetics ; Epithelial-Mesenchymal Transition ; Humans ; Induced Pluripotent Stem Cells ; cytology

Animals ; Cellular Reprogramming ; genetics ; DNA Transposable Elements ; genetics ; Genetic Vectors ; genetics ; Genome ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Mutagenesis

Animals ; Astrocytes ; cytology ; Cell Differentiation ; Cellular Reprogramming ; Induced Pluripotent Stem Cells ; cytology ; Kruppel-Like Transcription Factors ; genetics ; metabolism ; Mice ; Neurons ; cytology ; Octamer Transcription Factor-3 ; genetics ; metabolism

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 reprogramming. Previously deemed impossible, this research 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 reprogramming 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 transcription factors. The conception that somatic cells possess the capacity to revert to an immature status brings about huge clinical implications including personalized therapy, drug screening and disease modeling. Although this technology has potential to revolutionize the medical field, it is still impeded by technical and biological obstacles. This review describes the effervescent changes in this field, addresses bottlenecks hindering its advancement and in conclusion, applies the latest findings to overcome these issues.
Animals ; Cell Fusion ; Cell Lineage ; genetics ; Cellular Reprogramming ; genetics ; Humans ; Nuclear Transfer Techniques ; Pluripotent Stem Cells ; cytology ; metabolism ; Transcription Factors ; metabolism

Currently, animal somatic cell reprogramming into the induced pluripotent stem cell (iPS) is one of the hottest research target in the field of cell biology. We focused on the analysis of telomerase reverse transcriptase (TERT) gene expression during goat somatic fibroblasts reprogramming, and investigated the relationship between the expression of TERT and the pluripotency of reprogrammed cells. RNA samples of fetal tissues isolated from Guanzhong milk goat fetus, and the induced goat reprogramming cell clones were used to determine the relative expression levels of TERT by the real-time RT-PCR method. Goat embryonic fibroblasts (GEF) collected from the Guanzhong milk goat with normal karyotype were induced by 4 transcription factors to become reprogramming cells. The expression of TERT in reprogramming cells was detected by Real-time RT-PCR. The results showed that the expression of TERT in testis tissue was higher than that in epithelial tissues (P < 0.01). The expression level of TERT was higher in AP staining positive cells than that in AP staining negative cells (P < 0.01). This result indicated that TERT activity played an important role in cell reprogramming.
Animals ; Cellular Reprogramming ; Fibroblasts ; cytology ; Gene Expression Regulation ; Goats ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; RNA-Directed DNA Polymerase ; genetics ; Telomerase ; metabolism

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (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 efficiency 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 cell 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 light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

Embryonic stem cell is promising for regenerative medicine. However, its application is hampered by the utilization of eggs in most established methods. Recently, a new pluripotent stem cell establishing method was reported that, mouse and human differentiated cells could be induced reprogrammed into a pluripotent state by expressing exogenetic stem factors such as Oct4, Sox2, et al, through retroviral transduction. This approach avoiding egg use is a great breakthrough not only in stem cell technology but also present theory hypothesis of reprogramming. Here these works were reviewed in this article. Both the mechanism of induced reprogramming and the prospects of induced pluripotent stem cells were discussed.
Animals ; Cell Differentiation ; genetics ; Cells, Cultured ; Cellular Reprogramming ; drug effects ; genetics ; Humans ; Octamer Transcription Factor-3 ; metabolism ; Pluripotent Stem Cells ; cytology ; Retroviridae ; genetics ; SOXB1 Transcription Factors ; metabolism ; Transduction, Genetic