User:L!ttleW0lf/Reprogramming
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In cell culture systems
Reprogramming can also be induced artificially through the introduction of exogenous factors, usually transcription factors. In this context, it often refers to the creation of induced pluripotent stem cells from mature cells such as adult fibroblasts. This allows the production of stem cells for biomedical research, such as research into stem cell therapies, without the use of embryos. It is carried out by the transfection of stem-cell associated genes into mature cells using viral vectors such as retroviruses.
History
The first person to successfully demonstrate reprogramming was John Gurdon, who in 1962 demonstrated that differentiated somatic cells could be reprogrammed back into an embryonic state when he managed to obtain swimming tadpoles following the transfer of differentiated intestinal epithelial cells into enucleated frog eggs.[1] For this achievement he received the 2012 Nobel Prize in Medicine alongside Shinya Yamanaka.[2] Yamanaka was the first to demonstrate (in 2006) that this somatic cell nuclear transfer or oocyte-based reprogramming process (see below), that Gurdon discovered, could be recapitulated (in mice) by defined factors (Oct4, Sox2, Klf4, and c-Myc) to generate induced pluripotent stem cells (iPSCs).[3] Other combinations of genes have also been used, including LIN25 and NANOG[4].[5]
Phases of reprogramming into iPSC
With the discovery that cell fate could be altered, the question of what progression of events occur to signify a cell reprogramming. As the final product of iPSC reprogramming was similar in morphology, proliferation, gene expression, pluripotency, and telomerase activity was way to determine what phase of reprogramming was needed.[6] Reprogramming is defined into three phase: initiation, maturation, and stabilization.[7]
Initiation
Variability
The properties of cells obtained after reprogramming can vary significantly, in particular among iPSCs.[8] Factors leading to variation in the performance of reprogramming and functional features of end products include genetic background, tissue source, reprogramming factor stoichiometry and stressors related to cell culture.[8]
Somatic cell nuclear transfer
An oocyte can reprogram an adult nucleus into an embryonic state after somatic cell nuclear transfer, so that a new organism can be developed from such cell.[9]
Reprogramming is distinct from development of a somatic epitype,[10] as somatic epitypes can potentially be altered after an organism has left the developmental stage of life.[11] During somatic cell nuclear transfer, the oocyte turns off tissue specific genes in the Somatic cell nucleus and turns back on embryonic specific genes.
References
- ^ Gurdon JB (December 1962). "The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles". Journal of Embryology and Experimental Morphology. 10: 622–40. PMID 13951335.
- ^ "The Nobel Prize in Physiology or Medicine – 2012 Press Release". Nobel Media AB. 8 October 2012.
- ^ Takahashi K, Yamanaka S (August 2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors" (PDF). Cell. 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174. S2CID 1565219.
- ^ Magalhães, João Pedro de; Ocampo, Alejandro (2022-06-01). "Cellular reprogramming and the rise of rejuvenation biotech". Trends in Biotechnology. 40 (6): 639–642. doi:10.1016/j.tibtech.2022.01.011. ISSN 0167-7799. PMID 35190201.
- ^ Baker M (2007-12-06). "Adult cells reprogrammed to pluripotency, without tumors". Nature Reports Stem Cells. doi:10.1038/stemcells.2007.124.
- ^ Takahashi, Kazutoshi; Tanabe, Koji; Ohnuki, Mari; Narita, Megumi; Ichisaka, Tomoko; Tomoda, Kiichiro; Yamanaka, Shinya (2007-11-30). "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors". Cell. 131 (5): 861–872. doi:10.1016/j.cell.2007.11.019. ISSN 0092-8674. PMID 18035408.
- ^ David, Laurent; Polo, Jose M. (2014-05-01). "Phases of reprogramming". Stem Cell Research. 12 (3): 754–761. doi:10.1016/j.scr.2014.03.007. ISSN 1873-5061.
- ^ a b Paull D, Sevilla A, Zhou H, Hahn AK, Kim H, Napolitano C, Tsankov A, Shang L, Krumholz K, Jagadeesan P, Woodard CM, Sun B, Vilboux T, Zimmer M, Forero E, Moroziewicz DN, Martinez H, Malicdan MC, Weiss KA, Vensand LB, Dusenberry CR, Polus H, Sy KT, Kahler DJ, Gahl WA, Solomon SL, Chang S, Meissner A, Eggan K, Noggle SA (September 2015). "Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells". Nature Methods. 12 (9): 885–92. doi:10.1038/nmeth.3507. PMID 26237226. S2CID 9889991.
- ^ Hochedlinger K, Jaenisch R (June 2006). "Nuclear reprogramming and pluripotency". Nature. 441 (7097): 1061–7. Bibcode:2006Natur.441.1061H. doi:10.1038/nature04955. PMID 16810240. S2CID 4304218.
- ^ Lahiri DK, Maloney B (2006). "Genes are not our destiny: the somatic epitype bridges between the genotype and the phenotype". Nature Reviews Neuroscience. 7 (12): 976. doi:10.1038/nrn2022-c1.
- ^ Mathers JC (June 2006). "Nutritional modulation of ageing: genomic and epigenetic approaches". Mechanisms of Ageing and Development. 127 (6): 584–9. doi:10.1016/j.mad.2006.01.018. PMID 16513160. S2CID 9187848.