While this combination is most conventional in producing iPSCs, each of the factors can be functionally replaced by related transcription factors, miRNAs, small molecules, or even non-related genes such as lineage specifiers. The original set of reprogramming factors (also dubbed Yamanaka factors) are the transcription factors Oct4 (Pou5f1), Sox2, Klf4 and cMyc. IPSCs are typically derived by introducing products of specific sets of pluripotency-associated genes, or "reprogramming factors", into a given cell type. (4) A small subset of the transfected cells become iPS cells and generate ES-like colonies. (3) Harvest and culture the cells according to ES cell culture, using mitotically inactivated feeder cells (lightgray). Red cells indicate the cells expressing the exogenous genes. (2) Transduce stem cell-associated genes into the cells by viral vectors. Ī scheme of the generation of induced pluripotent stem (IPS) cells. In his Nobel seminar, Yamanaka cited the earlier seminal work of Harold Weintraub on the role of myoblast determination protein 1 (MyoD) in reprogramming cell fate to a muscle lineage as an important precursor to the discovery of iPSCs. Yamanaka named iPSCs with a lower case "i" due to the popularity of the iPod and other products. While the iPSC technology has not yet advanced to a stage where therapeutic transplants have been deemed safe, iPSCs are readily being used in personalized drug discovery efforts and understanding the patient-specific basis of disease. These unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection. Since iPSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line. Patient-matched embryonic stem cell lines can now be derived using somatic cell nuclear transfer (SCNT). However, since the generation of embryonic stem cells involves destruction (or at least manipulation) of the pre-implantation stage embryo, there has been much controversy surrounding their use. The most well-known type of pluripotent stem cell is the embryonic stem cell. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease. Pluripotent stem cells hold promise in the field of regenerative medicine. Shinya Yamanaka was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent." The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Japan, who together showed in 2006 that the introduction of four specific genes (named Myc, Oct3/4, Sox2 and Klf4), collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. Only those cells comprising the center colony are human iPS cells. The spindle-shaped cells in the background are mouse fibroblast cells.
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