Human embryonic stem cells are pluripotent cells derived from the inner cell mass of blastocyst-stage embryos. These cells possess two unique properties: an indefinite self-renewal capacity and pluripotency, the ability to differentiate to cells from the three germ layers. The pathways governing self-renewal and pluripotency are currently under intensive research. Much effort is devoted to the establishment of feeder-free cultures by elucidation of the cytokines and growth factors required for cell propagation. These seem thus far, to be distinct from those required by mouse embryonic stem cells. In addition, transcriptional regulators unique to embryonic stem cells seem to govern the pluripotent state. These transcriptional regulators determine cell fate, and decide whether the cell will remain pluripotent or differentiate. Together, the understanding of the exogenous and endogenous factors determining cell fate will facilitate the use of these cells in cell-based therapies and will allow understanding of early developmental processes.
"ESCs are maintained in a state of pluripotency by a precise regulation of numerous intrinsic and extrinsic factors. In hESCs, Fibroblast growth factor (FGF), activin, and Bone morphogenetic signaling (BMP) signaling have been shown to be critical in maintaining self-renewal . In addition, intrinsic factors such as OCT3/4, SOX2, and NANOG are generally regarded as the central core of genes that keep hESCs in an undifferentiated state capable of indefinite self-renewal . "
[Show abstract][Hide abstract] ABSTRACT: Reprogramming human somatic cells to pluripotency represents a valuable resource for the development of in vitro based models for human disease and holds tremendous potential for deriving patient-specific pluripotent stem cells. Recently, mouse neural stem cells (NSCs) have been shown capable of reprogramming into a pluripotent state by forced expression of Oct3/4 and Klf4; however it has been unknown whether this same strategy could apply to human NSCs, which would result in more relevant pluripotent stem cells for modeling human disease.
Here, we show that OCT3/4 and KLF4 are indeed sufficient to induce pluripotency from human NSCs within a two week time frame and are molecularly indistinguishable from human ES cells. Furthermore, human NSC-derived pluripotent stem cells can differentiate into all three germ lineages both in vitro and in vivo.
We propose that human NSCs represent an attractive source of cells for producing human iPS cells since they only require two factors, obviating the need for c-MYC, for induction into pluripotency. Thus, in vitro human disease models could be generated from iPS cells derived from human NSCs.
PLoS ONE 09/2009; 4(9):e7044. DOI:10.1371/journal.pone.0007044 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ever since the derivation of the first human embryonic stem cell line, hopes have persisted for the treatment of a wide range of cellular degenerative diseases. However, significant immuno-incompatibility between donor cells and recipient patients remains an unsolved challenge. Currently, three main strategies are investigated in humans to create autologous pluripotent stem cells: somatic cell nuclear transfer, cell fusion and cell extract incubation. All methods exploit the fact that a somatic genome is amenable to epigenetic dedifferentiation into a more plastic state, presumably through direct exposure to and manipulation by heterologous transcriptional factors. Epigenetic reprogramming includes profound modifications of chromatin structure, but the responsible mechanisms that work in toti- and pluripotent cells remain largely unknown. This review presents a brief introduction to stem cell terminology and epigenetics, followed by a critical examination of the predominant methodologies involved. Finally, the search for specific reprogramming factors is discussed, and obstacles for the clinical implementation of reprogrammed cells are addressed.
Regenerative Medicine 10/2007; 2(5):795-816. DOI:10.2217/174607126.96.36.1995 · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The development of porcine embryonic stem cell lines (pESC) has received renewed interest given the advances being made in the production of immunocompatible transgenic pigs. However, difficulties are evident in the production of pESCs in-vitro. This may largely be attributable to differences in porcine pre-implantation development compared to the mouse and human. Expression of oct4, nanog and sox2 differs in the zona-enclosed porcine blastocyst compared to its mouse and human counterparts, which may suggest that other factors may be responsible for maintaining porcine pluripotency in the early blastocyst. In addition, the epiblast forms considerably later, at days 7 to 8 when the porcine blastocyst begins to hatch and is maintained for 4 days before completely differentiating. This review covers an outline of the known molecular profile during porcine pre-implantation development and provides a history in the development of putative pESCs to date. Greater knowledge on the molecular mechanisms that underlie porcine pluripotency and pre-implantation development may aid in improving the development of pESCs.
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