Editing Oct-4 (section)

==Role in reprogramming==

Oct-4 is one of the transcription factors that is used to create [[induced pluripotent stem cell]]s (iPSCs), together with [[Sox2]],  [[Kruppel-like factors|Klf4]], and often c-[[Myc]] (OSKM) in mice,<ref>{{cite journal | vauthors = Okita K, Ichisaka T, Yamanaka S | title = Generation of germline-competent induced pluripotent stem cells | journal = Nature | volume = 448 | issue = 7151 | pages = 313–7 | date = July 2007 | pmid = 17554338 | doi = 10.1038/nature05934 | bibcode = 2007Natur.448..313O | s2cid = 459050 }}</ref><ref>{{cite journal | vauthors = Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R | title = In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state | journal = Nature | volume = 448 | issue = 7151 | pages = 318–24 | date = July 2007 | pmid = 17554336 | doi = 10.1038/nature05944 | bibcode = 2007Natur.448..318W | s2cid = 4377572 }}</ref><ref>{{cite journal | vauthors = Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K | title = Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution | journal = Cell Stem Cell | volume = 1 | issue = 1 | pages = 55–70 | date = June 2007 | pmid = 18371336 | doi = 10.1016/j.stem.2007.05.014 | doi-access = free }}</ref> demonstrating its capacity to induce an embryonic stem-cell-like state. These factors are often referred to as "[[Yamanaka factors|Yamanaka reprogramming factors]]". This reprogramming effect has also been seen with the [[Thomson reprogramming factors]], reverting human fibroblast cells to iPSCs via Oct-4, along with Sox2, [[Homeobox protein NANOG|Nanog]], and [[LIN28|Lin28]]. The use of Thomson reprogramming factors avoids the need to overexpress c-Myc, an oncogene.<ref>{{cite journal | vauthors = Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA | title = Induced pluripotent stem cell lines derived from human somatic cells | journal = Science | volume = 318 | issue = 5858 | pages = 1917–20 | date = December 2007 | pmid = 18029452 | doi = 10.1126/science.1151526 | bibcode = 2007Sci...318.1917Y | s2cid = 86129154 }}</ref>  It was later determined that only two of these four factors, namely Oct4 and Klf4, are sufficient to reprogram mouse adult neural stem cells.<ref name="pmid18594515">{{cite journal | vauthors = Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Araúzo-Bravo MJ, Ruau D, Han DW, Zenke M, Schöler HR | title = Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors | journal = Nature | volume = 454 | issue = 7204 | pages = 646–50 | date = July 2008 | pmid = 18594515 | doi = 10.1038/nature07061 | bibcode = 2008Natur.454..646K | s2cid = 4318637 }}</ref>  Finally it was shown that a single factor, Oct-4 was sufficient for this transformation.<ref name="Kim_2009">{{cite journal | vauthors = Kim JB, Sebastiano V, Wu G, Araúzo-Bravo MJ, Sasse P, Gentile L, Ko K, Ruau D, Ehrich M, van den Boom D, Meyer J, Hübner K, Bernemann C, Ortmeier C, Zenke M, Fleischmann BK, Zaehres H, Schöler HR | title = Oct4-induced pluripotency in adult neural stem cells | journal = Cell | volume = 136 | issue = 3 | pages = 411–9 | date = February 2009 | pmid = 19203577 | doi = 10.1016/j.cell.2009.01.023 | s2cid = 1630949 | doi-access = free }}</ref> Moreover, while Sox2, Klf4, and cMyc could be replaced by their respective family members, Oct4's closer relatives, [[POU2F1|Oct1]] and [[Oct6]], fail to induce pluripotency, thus demonstrating the exclusiveness of Oct4 among POU transcription factors.<ref>{{cite journal | vauthors = Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S | title = Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts | journal = Nature Biotechnology | volume = 26 | issue = 1 | pages = 101–6 | date = January 2008 | pmid = 18059259 | doi = 10.1038/nbt1374 | s2cid = 1705950 }}</ref> However, later it was shown that Oct4 could be completely omitted from the Yamanaka cocktail, and the remaining three factors, Sox2, Klf4, and cMyc (SKM) could generate mouse iPSCs with dramatically enhanced developmental potential.<ref>{{cite journal | vauthors = Velychko S, Adachi K, Kim KP, Hou Y, MacCarthy CM, Wu G, Schöler HR | title = Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs | journal = Cell Stem Cell | volume = 25 | issue = 6 | pages = 737–753.e4 | date = December 2019 | pmid = 31708402 | doi = 10.1016/j.stem.2019.10.002 | pmc = 6900749 | doi-access = free }}</ref> This suggests that Oct4 increases the efficiency of reprogramming, but decreases the quality of resulting iPSCs. This is possibly due to a mutated OCT4 DBD cysteine residue (Cys48) that has been identified as a central reprogramming determinant.<ref name = "Shen_2024">{{cite journal | vauthors = Shen Z, Wu Y, Manna A, Yi C, Cairns BR, Evason KJ, Chandrasekharan MB, Tantin D | title = Oct4 redox sensitivity potentiates reprogramming and differentiation | journal = Genes & Development | volume = 38 | issue = 7–8 | pages = 308–321 | date = May 2024 | pmid = 38719541 | doi = 10.1101/gad.351411.123 | pmc = 11146590 }}</ref> The serine residue in OCT1 is mutated in the presence of the OCT4 N terminus, which conversely causes OCT4's serine (converted from cysteine) to reduce reprogramming efficiency by 60%.<ref name = "Shen_2024" />