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Induced stem cells (iSC) are stem cells artificially derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotent—iMSC, also called an induced multipotent progenitor cell—iMPC) or unipotent -- (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells. Three techniques are widely recognized: * Transplantation of nuclei taken from somatic cells into an oocyt (egg cell) lacking its own nucleus (removed in lab) 〔Gurdon J. B. and Ian Wilmut (2011) Nuclear Transfer to Eggs and Oocytes Cold Spring Harb Perspect Biol; 3: a002659〕 * Fusion of somatic cells with pluripotent stem cells and * Modification of somatic cells, inducing its transformation into a stem cell, using: the genetic material encoding reprogramming protein factors, recombinant proteins; microRNA, a synthetic, self-replicating polycistronic RNA, and low-molecular weight biologically active substances.〔 〕〔 〕 == Natural processes of induction == In 1895 Thomas Morgan removed one of the two frog blastomeres and found that amphibians are able to form whole embryo from the remaining part. This meant that the cells can change their differentiation pathway. Later, in 1924, Spemann and Mangold demonstrated the key importance of cell–cell inductions during animal development.〔(Box 3 ) FROM THE ARTICLE: Edward M. De Robertis (2006). ''Nature Reviews Molecular Cell Biology'' 7, 296-302 〕 The reversible transformation of cells of one differentiated cell type to another is called metaplasia. This transition can be a part of the normal maturation process, or caused by an inducing stimulus. For example: transformation of iris cells to lens cells in the process of maturation and transformation of retinal pigment epithelium cells into the neural retina during regeneration in adult newt eyes. This process allows the body to replace cells not suitable to new conditions with more suitable new cells. In Drosophila imaginal discs, cells have to choose from a limited number of standard discrete differentiation states. The fact that transdetermination (change of the path of differentiation) often occurs for a group of cells rather than single cells shows that it is induced rather than part of maturation.〔 〕 The researchers were able to identify the minimal conditions and factors that would be sufficient for starting the cascade of molecular and cellular processes to instruct pluripotent cells to organize the embryo. They showed that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, ''in vivo'' or ''in vitro'', uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.〔Peng-Fei Xu, Nathalie Houssin, Karine F. Ferri-Lagneau, Bernard Thisse and Christine Thisse. (April 2014). Construction of a Vertebrate Embryo from Two Opposing Morphogen Gradients. Science: 344(6179), 87-89 〕 Some types of mature, specialized adult cells can naturally revert to stem cells. For example, "chief" cells express the stem cell marker Troy. While they normally produce digestive fluids for the stomach, they can revert into stem cells to make temporary repairs to stomach injuries, such as a cut or damage from infection. Moreover, they can make this transition even in the absence of noticeable injuries and are capable of replenishing entire gastric units, in essence serving as quiescent “reserve” stem cells. Differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves, and then differentiate into the cell types needing replacement in the damaged tissue Macrophages can self-renew by local proliferation of mature differentiated cells. In newts, muscle tissue is regenerated from specialized muscle cells that dedifferentiate and forget the type of cell they had been. This capacity to regenerate does not decline with age and may be linked to their ability to make new stem cells from muscle cells on demand. A variety of nontumorigenic stem cells display the ability to generate multiple cell types. For instance, multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant adult human stem cells that can self-renew. They form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency and can differentiate into endodermal, ectodermal and mesodermal cells both in vitro and in vivo.〔Ogura F, Wakao S, Kuroda Y, Tsuchiyama K, Bagheri M, Heneidi S, Chazenbalk G, Aiba S, Dezawa M. (2014). (Human Adipose Tissue Possesses a Unique Population of Pluripotent Stem Cells with Nontumorigenic and Low Telomerase Activities: Potential Implications in Regenerative Medicine ). Stem Cells Dev. Epub ahead of print〕 Other well-documented examples of transdifferentiation and their significance in development and regeneration were described in detail. 抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)』 ■ウィキペディアで「Induced stem cells」の詳細全文を読む スポンサード リンク
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