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Pluripotent Stem Cells: Recent Progress and Challenges

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Pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) and induced PSCs (iPSCs) have unlimited ability for self-renewal and can be differentiated into cells of all three germ layers. ESCs are originated from the inner cell mass (ICM) of blastocyst-stage embryos, while iPSCs are generated by ...

Pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) and induced PSCs (iPSCs) have unlimited ability for self-renewal and can be differentiated into cells of all three germ layers. ESCs are originated from the inner cell mass (ICM) of blastocyst-stage embryos, while iPSCs are generated by reprogramming of somatic cells to a pluripotent state through enforced expression of a group of key transcription factors. Sustaining pluripotency is one of the most critical characteristics of PSCs. Recently, substantial progress has been made in identifying endogenous factors, which control PSC pluripotency. These factors, such as Oct4, Nanog and Sox2, activate target genes that encode pluripotency and suppress signaling pathways inducing differentiation. Furthermore, the control of cell fates through cellular reprogramming has changed fundamental thoughts about the fixed cell identity, which stimulates new methods in research into human disease modeling and cell differentiation.
The establishment of hiPSCs from patients suffering from a certain disease is crucial to be used as a material to study the pathogenesis of the disease. Several studies have recently described the generation of iPSC lines from patients with different types of diseases. Somatic cell nuclear transfer (SCNT) is another mean to generate personalized PSCs from somatic cells of the patients. Interestingly, patient-specific hESCs have recently been generated using SCNT technology. Recent advances in somatic cell reprogramming to iPSCs as well as successful generation of ESCs from somatic cells open new avenues in generating disease-specific PSC lines, which offer a novel method for modeling human diseases, drug discovery screening, and ultimately personalized regenerative medicine.
However, there are several challenges facing the use of PSCs in clinical applications. For example, hESCs are still facing difficulties associated with ethical issues and their immunological incompatibility. Furthermore, it has been found that although during PSC differentiation most of the pluripotency genes are efficiently downregulated, some genes, typically associated with early embryos, continue to be expressed in the differentiated cells, suggesting that the cells derived from PSCs are equal to those found during early embryonic development. Another issue is the genomic stability of iPSCs since some studies identified mutations in iPSC genome. Therefore, the future studies of ESCs concurrently with iPSCs are important in getting the basic knowledge to address the difficulties facing their use for in vitro disease modeling and therapeutic applications.
Goal of this Research Topic is to provide a platform for publishing original articles and reviews focus on the recent advances and challenges in the use of PSCs in disease modeling and regenerative medicine as well as the recent progress in pluripotency, reprogramming, differentiation, epigenetics, and genomics of PSCs.


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