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Xin-Chun Yang, Xiao-Long Wu, Wen-Hao Li, Xiao-Jie Wu, Qiao-Yan Shen, Yun-Xiang Li, Sha Peng, Jin-Lian Hua. OCT6 inhibits differentiation of porcine-induced pluripotent stem cells through MAPK and PI3K signaling regulation. Zoological Research, 2022, 43(6): 911-922. doi: 10.24272/j.issn.2095-8137.2022.220
Citation: Xin-Chun Yang, Xiao-Long Wu, Wen-Hao Li, Xiao-Jie Wu, Qiao-Yan Shen, Yun-Xiang Li, Sha Peng, Jin-Lian Hua. OCT6 inhibits differentiation of porcine-induced pluripotent stem cells through MAPK and PI3K signaling regulation. Zoological Research, 2022, 43(6): 911-922. doi: 10.24272/j.issn.2095-8137.2022.220

OCT6 inhibits differentiation of porcine-induced pluripotent stem cells through MAPK and PI3K signaling regulation

doi: 10.24272/j.issn.2095-8137.2022.220
#Authors contributed equally to this work
Funds:  This work was supported by the National Natural Science Foundation of China (32072806), Shaanxi Province Science and Technology Innovation Team Project (2019TD-036), and Shaanxi Province Science and Technology Project (2022NY-044)
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  • Corresponding author: E-mail: jinlianhua@nwsuaf.edu.cn
  • Received Date: 2022-07-01
  • Accepted Date: 2022-09-01
  • Published Online: 2022-09-02
  • As a transcription factor of the Pit-Oct-Unc (POU) domain family, octamer-binding transcription factor 6 (OCT6) participates in various aspects of stem cell development and differentiation. At present, however, its role in porcine-induced pluripotent stem cells (piPSCs) remains unclear. Here, we explored the function of OCT6 in piPSCs. We found that piPSCs overexpressing OCT6 maintained colony morphology and pluripotency under differentiation conditions, with a similar gene expression pattern to that of non-differentiated piPSCs. Functional analysis revealed that OCT6 attenuated the adverse effects of extracellular signal-regulated kinase (ERK) signaling pathway inhibition on piPSC pluripotency by activating phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling activity. Our research sheds new light on the mechanism by which OCT6 promotes PSC maintenance.
  • #Authors contributed equally to this work
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  • [1]
    Aoki M, Fujishita T. 2017. Oncogenic roles of the PI3K/AKT/mTOR axis. In: Hunter E, Bister K. Viruses, Genes, and Cancer. Cham: Springer, 153–189.
    [2]
    Armstrong L, Hughes O, Yung S, Hyslop L, Stewart R, Wappler I, et al. 2006. The role of PI3K/AKT, MAPK/ERK and NFκβ signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis. Human Molecular Genetics, 15(11): 1894−1913. doi: 10.1093/hmg/ddl112
    [3]
    Baghdadi MB, Castel D, Machado L, Fukada SI, Birk DE, Relaix F, et al. 2018. Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche. Nature, 557(7707): 714−718. doi: 10.1038/s41586-018-0144-9
    [4]
    Bao SD, Wu QL, Li ZZ, Sathornsumetee S, Wang H, McLendon RE, et al. 2008. Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Research, 68(15): 6043−6048. doi: 10.1158/0008-5472.CAN-08-1079
    [5]
    Berthelsen MF, Riedel M, Cai HQ, Skaarup SH, Alstrup AKO, Dagnæs-Hansen F, et al. 2021. The CRISPR/Cas9 minipig-a transgenic minipig to produce specific mutations in designated tissues. Cancers, 13(12): 3024. doi: 10.3390/cancers13123024
    [6]
    Blick C, Ramachandran A, Wigfield S, McCormick R, Jubb A, Buffa FM, et al. 2013. Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer. British Journal of Cancer, 109(1): 50−59. doi: 10.1038/bjc.2013.240
    [7]
    Chen J, Shu S, Chen YT, Liu Z, Yu LJ, Yang LX, et al. 2019. AIM2 deletion promotes neuroplasticity and spatial memory of mice. Brain Research Bulletin, 152: 85−94. doi: 10.1016/j.brainresbull.2019.07.011
    [8]
    Choi J, Huebner AJ, Clement K, Walsh RM, Savol A, Lin KX, et al. 2017. Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells. Nature, 548(7666): 219−223. doi: 10.1038/nature23274
    [9]
    Corsinotti A, Wong FCK, Tatar T, Szczerbinska I, Halbritter F, Colby D, et al. 2017. Distinct SoxB1 networks are required for naïve and primed pluripotency. eLife, 6: e27746. doi: 10.7554/eLife.27746
    [10]
    Cui R, Cao GM, Bai HM, Zhang ZY. 2019. LPAR1 regulates the development of intratumoral heterogeneity in ovarian serous cystadenocarcinoma by activating the PI3K/AKT signaling pathway. Cancer Cell International, 19: 201. doi: 10.1186/s12935-019-0920-0
    [11]
    Ding VMY, Ling L, Natarajan S, Yap MGS, Cool SM, Choo ABH. 2010. FGF-2 modulates Wnt signaling in undifferentiated hESC and iPS cells through activated PI3-K/GSK3β signaling. Journal of Cellular Physiology, 225(2): 417−428. doi: 10.1002/jcp.22214
    [12]
    Esteban MA, Xu JY, Yang JY, Peng MX, Qin DJ, Li W, et al. 2009. Generation of induced pluripotent stem cell lines from Tibetan miniature pig. Journal of Biological Chemistry, 284(26): 17634−17640. doi: 10.1074/jbc.M109.008938
    [13]
    Ezashi T, Telugu BPVL, Alexenko AP, Sachdev S, Sinha S, Roberts RM. 2009. Derivation of induced pluripotent stem cells from pig somatic cells. Proceedings of the National Academy of Sciences of the United States of America, 106(27): 10993−10998. doi: 10.1073/pnas.0905284106
    [14]
    Friedrich RP, Schlierf B, Tamm ER, Bösl MR, Wegner M. 2005. The class III POU domain protein Brn-1 can fully replace the related Oct-6 during schwann cell development and myelination. Molecular and Cellular Biology, 25(5): 1821−1829. doi: 10.1128/MCB.25.5.1821-1829.2005
    [15]
    Gao Y, Guo YJ, Duan AQ, Cheng D, Zhang SQ, Wang HY. 2014. Optimization of culture conditions for maintaining porcine induced pluripotent stem cells. DNA and Cell Biology, 33(1): 1−11. doi: 10.1089/dna.2013.2095
    [16]
    Gong CC, Hu Y, Zhou M, Yao MJ, Ning ZX, Wang Z, et al. 2019. Identification of specific modules and hub genes associated with the progression of gastric cancer. Carcinogenesis, 40(10): 1269−1277. doi: 10.1093/carcin/bgz040
    [17]
    Gorczyca G, Wartalski K, Wiater J, Samiec M, Tabarowski Z, Duda M. 2021. Anabolic steroids-driven regulation of porcine ovarian putative stem cells favors the onset of their neoplastic transformation. International Journal of Molecular Sciences, 22(21): 11800. doi: 10.3390/ijms222111800
    [18]
    Hackett JA, Surani MA. 2014. Regulatory principles of pluripotency: from the ground state up. Cell Stem Cell, 15(4): 416−430. doi: 10.1016/j.stem.2014.09.015
    [19]
    Haddadi N, Lin YG, Travis G, Simpson AM, Nassif NT, McGowan EM. 2018. PTEN/PTENP1: 'Regulating the regulator of RTK-dependent PI3K/Akt signalling', new targets for cancer therapy. Molecular Cancer, 17(1): 37. doi: 10.1186/s12943-018-0803-3
    [20]
    Hiratsuka T, Bordeu I, Pruessner G, Watt FM. 2020. Regulation of ERK basal and pulsatile activity control proliferation and exit from the stem cell compartment in mammalian epidermis. Proceedings of the National Academy of Sciences of the United States of America, 117(30): 17796−17807. doi: 10.1073/pnas.2006965117
    [21]
    Jauch R, Choo SH, Ng CKL, Kolatkar PR. 2011. Crystal structure of the dimeric oct6 (POU3f1) POU domain bound to palindromic more DNA. Proteins, 79(2): 674−677. doi: 10.1002/prot.22916
    [22]
    Jerabek S, Ng CKL, Wu GM, Arauzo-Bravo MJ, Kim KP, Esch D, et al. 2017. Changing POU dimerization preferences converts oct6 into a pluripotency inducer. EMBO Reports, 18(2): 319−333. doi: 10.15252/embr.201642958
    [23]
    Kawasaki T, Oka N, Tachibana H, Akiguchi I, Shibasaki H. 2003. oct6, a transcription factor controlling myelination, is a marker for active nerve regeneration in peripheral neuropathies. Acta Neuropathologica, 105(3): 203−208. doi: 10.1007/s00401-002-0630-9
    [24]
    Kim KP, Choi J, Yoon J, Bruder JM, Shin B, Kim J, et al. 2021. Permissive epigenomes endow reprogramming competence to transcriptional regulators. Nature Chemical Biology, 17(1): 47−56. doi: 10.1038/s41589-020-0618-6
    [25]
    Kim KP, Wu Y, Yoon J, Adachi K, Wu GM, Velychko S, et al. 2020. Reprogramming competence of OCT factors is determined by transactivation domains. Science Advances, 6(36): eaaz7364. doi: 10.1126/sciadv.aaz7364
    [26]
    Kuhlbrodt K, Herbarth B, Sock E, Enderich J, Hermans-Borgmeyer I, Wegner M. 1998. Cooperative function of POU proteins and SOX proteins in glial cells. Journal of Biological Chemistry, 273(26): 16050−16057. doi: 10.1074/jbc.273.26.16050
    [27]
    Leng C, Zhang ZG, Chen WX, Luo HP, Song J, Dong W, et al. 2016. An integrin beta4-EGFR unit promotes hepatocellular carcinoma lung metastases by enhancing anchorage independence through activation of FAK-AKT pathway. Cancer Letters, 376(1): 188−196. doi: 10.1016/j.canlet.2016.03.023
    [28]
    Li N, Yan YL, Fu S, Li RJ, Zhao PF, Xu XY, et al. 2017a. Lysophosphatidic acid enhances human umbilical cord mesenchymal stem cell viability without differentiation via LPA receptor mediating manner. Apoptosis, 22(10): 1296−1309. doi: 10.1007/s10495-017-1399-6
    [29]
    Li XL, Liu L, Li DD, He YP, Guo LH, Sun LP, et al. 2017b. Integrin β4 promotes cell invasion and epithelial-mesenchymal transition through the modulation of Slug expression in hepatocellular carcinoma. Scientific Reports, 7: 40464. doi: 10.1038/srep40464
    [30]
    Li ZY, Li XH, Tian GW, Zhang DY, Gao H, Wang ZY. 2019. MAGI1 inhibits the proliferation, migration and invasion of glioma cells. OncoTargets and Therapy, 12: 11281−11290. doi: 10.2147/OTT.S230236
    [31]
    Ma YY, Yu T, Cai YX, Wang HY. 2018. Preserving self-renewal of porcine pluripotent stem cells in serum-free 3i culture condition and independent of LIF and b-FGF cytokines. Cell Death Discovery, 4: 21.
    [32]
    Malik V, Glaser LV, Zimmer D, Velychko S, Weng MX, Holzner M, et al. 2019. Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2. Nature Communications, 10(1): 3477. doi: 10.1038/s41467-019-11054-7
    [33]
    Mansouri A, Hallonet M, Gruss P. 1996. Pax genes and their roles in cell differentiation and development. Current Opinion in Cell Biology, 8(6): 851−857. doi: 10.1016/S0955-0674(96)80087-1
    [34]
    Meijer D, Graus A, Kraay R, Langeveld A, Mulder MP, Grosveld G. 1990. The octamer binding factor oct6: cDNA cloning and expression in early embryonic cells. Nucleic Acids Research, 18(24): 7357−7365. doi: 10.1093/nar/18.24.7357
    [35]
    Michael JV, Wurtzel JGT, Goldfinger LE. 2016. Regulation of H-Ras-driven MAPK signaling, transformation and tumorigenesis, but not PI3K signaling and tumor progression, by plasma membrane microdomains. Oncogenesis, 5(5): e228. doi: 10.1038/oncsis.2016.36
    [36]
    Montserrat N, De Oñate L, Garreta E, Gonzãlez F, Adamo A, Eguizãbal C, et al. 2012. Generation of feeder-free pig induced pluripotent stem cells without Pou5f1. Cell Transplantation, 21(5): 815−825. doi: 10.3727/096368911X601019
    [37]
    Oh GS, Yoon J, Kim G, Kim GH, Kim DS, Choi B, et al. 2020. Regulation of adipocyte differentiation by clusterin-mediated Krüppel-like factor 5 stabilization. The FASEB Journal, 34(12): 16276−16290. doi: 10.1096/fj.202000551RR
    [38]
    Olivera R, Moro LN, Jordan R, Luzzani C, Miriuka S, Radrizzani M, et al. 2016. In vitro and in vivo development of horse cloned embryos generated with iPSCs, mesenchymal stromal cells and fetal or adult fibroblasts as nuclear donors. PLoS One, 11(10): e0164049. doi: 10.1371/journal.pone.0164049
    [39]
    Podstawski P, Samiec M, Skrzyszowska M, Szmatoła T, Semik-Gurgul E, Ropka-Molik K. 2022. The induced expression of BPV E4 gene in equine adult dermal fibroblast cells as a potential model of skin sarcoid-like Neoplasia. International Journal of Molecular Sciences, 23(4): 1970. doi: 10.3390/ijms23041970
    [40]
    Samiec M, Skrzyszowska M. 2010. Preimplantation developmental capability of cloned pig embryos derived from different types of nuclear donor somatic cells. Annals of Animal Science, 10(4): 385−398.
    [41]
    Secher JO, Liu Y, Petkov S, Luo YL, Li D, Hall VJ, et al. 2017. Evaluation of porcine stem cell competence for somatic cell nuclear transfer and production of cloned animals. Animal Reproduction Science, 178: 40−49. doi: 10.1016/j.anireprosci.2017.01.007
    [42]
    Singh AM, Reynolds D, Cliff T, Ohtsuka S, Mattheyses AL, Sun YH, et al. 2012. Signaling network crosstalk in human pluripotent cells: a Smad2/3-regulated switch that controls the balance between self-renewal and differentiation. Cell Stem Cell, 10(3): 312−326. doi: 10.1016/j.stem.2012.01.014
    [43]
    Sock E, Enderich J, Rosenfeld MG, Wegner M. 1996. Identification of the nuclear localization signal of the POU domain protein Tst-1/oct6. Journal of Biological Chemistry, 271(29): 17512−17518. doi: 10.1074/jbc.271.29.17512
    [44]
    Son YS, Seong RH, Ryu CJ, Cho YS, Bae KH, Chung SJ, et al. 2011. Brief report: L1 cell adhesion molecule, a novel surface molecule of human embryonic stem cells, is essential for self-renewal and pluripotency. Stem Cells, 29(12): 2094−2099. doi: 10.1002/stem.754
    [45]
    Song H, Li H, Huang MR, Xu D, Wang ZY, Wang F. 2016. Big animal cloning using transgenic induced pluripotent stem cells: a case study of goat transgenic induced pluripotent stem cells. Cellular Reprogramming, 18(1): 37−47. doi: 10.1089/cell.2015.0035
    [46]
    Su PH, Lin YW, Huang RL, Liao YP, Lee HY, Wang HC, et al. 2013. Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer. Oncogene, 32(1): 15−26. doi: 10.1038/onc.2012.29
    [47]
    Teichroeb JH, Betts DH, Vaziri H. 2011. Suppression of the imprinted gene NNAT and X-chromosome gene activation in isogenic human iPS cells. PLoS One, 6(10): e23436. doi: 10.1371/journal.pone.0023436
    [48]
    Wei YD, Du XM, Yang DH, Ma FL, Yu XW, Zhang MF, et al. 2021. Dmrt1 regulates the immune response by repressing the TLR4 signaling pathway in goat male germline stem cells. Zoological Research, 42(1): 14−27. doi: 10.24272/j.issn.2095-8137.2020.186
    [49]
    Welham MJ, Kingham E, Sanchez-Ripoll Y, Kumpfmueller B, Storm M, Bone H. 2011. Controlling embryonic stem cell proliferation and pluripotency: the role of PI3K- and GSK-3-dependent signalling. Biochemical Society Transactions, 39(2): 674−678. doi: 10.1042/BST0390674
    [50]
    Wen XM, Jiao LD, Tan H. 2022. MAPK/ERK pathway as a central regulator in vertebrate organ regeneration. International Journal of Molecular Sciences, 23(3): 1464. doi: 10.3390/ijms23031464
    [51]
    Wiater J, Samiec M, Skrzyszowska M, Lipiński D. 2021a. Trichostatin A-assisted epigenomic modulation affects the expression profiles of not only recombinant human α1, 2-fucosyltransferase and α-galactosidase A enzymes but also Galα1→3Gal epitopes in porcine Bi-transgenic adult cutaneous fibroblast cells. International Journal of Molecular Sciences, 22(3): 1386. doi: 10.3390/ijms22031386
    [52]
    Wiater J, Samiec M, Wartalski K, Smorąg Z, Jura J, Słomski R, et al. 2021b. Characterization of mono- and Bi-transgenic pig-derived epidermal keratinocytes expressing human FUT2 and GLA genes-in vitro studies. International Journal of Molecular Sciences, 22(18): 9683. doi: 10.3390/ijms22189683
    [53]
    Wolfrum K, Wang Y, Prigione A, Sperling K, Lehrach H, Adjaye J. 2010. The LARGE principle of cellular reprogramming: lost, acquired and retained gene expression in foreskin and amniotic fluid-derived human iPS cells. PLoS One, 5(10): e13703. doi: 10.1371/journal.pone.0013703
    [54]
    Wu DY, Yao Z. 2005. Isolation and characterization of the murine Nanog gene promoter. Cell Research, 15(5): 317−324. doi: 10.1038/sj.cr.7290300
    [55]
    Wu X, Oatley JM, Oatley MJ, Kaucher AV, Avarbock MR, Brinster RL. 2010. The POU domain transcription factor POU3F1 is an important intrinsic regulator of GDNF-induced survival and self-renewal of mouse spermatogonial stem cells. Biology of Reproduction, 82(6): 1103−1111. doi: 10.1095/biolreprod.109.083097
    [56]
    Wu XL, Zhu ZS, Xiao X, Zhou Z, Yu S, Shen QY, et al. 2021. LIN28A inhibits DUSP family phosphatases and activates MAPK signaling pathway to maintain pluripotency in porcine induced pluripotent stem cells. Zoological Research, 42(3): 377−388. doi: 10.24272/j.issn.2095-8137.2020.375
    [57]
    Xu JJ, Yu LQ, Guo JX, Xiang JZ, Zheng Z, Gao DF, et al. 2019. Generation of pig induced pluripotent stem cells using an extended pluripotent stem cell culture system. Stem Cell Research & Therapy, 10(1): 193.
    [58]
    Xu K, Zhang XL, Liu ZG, Ruan JX, Xu CJ, Che JJ, et al. 2022. A transgene-free method for rapid and efficient generation of precisely edited pigs without monoclonal selection. Science China Life Sciences, 65(8): 1535−1546. doi: 10.1007/s11427-021-2058-2
    [59]
    Yao X, Tan Z, Gu B, Wu RR, Liu YK, Dai LC, et al. 2010. Promotion of self-renewal of embryonic stem cells by midkine. Acta Pharmacologica Sinica, 31(5): 629−637. doi: 10.1038/aps.2010.39
    [60]
    Yu JH, Liu D, Sun XJ, Yang K, Yao JF, Cheng C, et al. 2019. CDX2 inhibits the proliferation and tumor formation of colon cancer cells by suppressing Wnt/β-catenin signaling via transactivation of GSK-3β and Axin2 expression. Cell Death & Disease, 10(1): 26.
    [61]
    Yu XW, Li TT, Du XM, Shen QY, Zhang MF, Wei YD, et al. 2021. Single-cell RNA sequencing reveals atlas of dairy goat testis cells. Zoological Research, 42(4): 401−405. doi: 10.24272/j.issn.2095-8137.2020.373
    [62]
    Zhang G, Chen HX, Yang SN, Zhao J. 2020a. MAGI1-IT1 stimulates proliferation in non-small cell lung cancer by upregulating AKT1 as a ceRNA. European Review for Medical and Pharmacological Sciences, 24(2): 691−698.
    [63]
    Zhang R, Yu S, Shen QY, Zhao WX, Zhang JQ, Wu XL, et al. 2021. AXIN2 reduces the survival of porcine induced pluripotent stem cells (piPSCs). International Journal of Molecular Sciences, 22(23): 12954. doi: 10.3390/ijms222312954
    [64]
    Zhang WJ, Zhang XY, Zhang L, Xu D, Cheng NN, Tang Y, et al. 2020b. Astrocytes increase exosomal secretion of oligodendrocyte precursor cells to promote their proliferation via integrin β4-mediated cell adhesion. Biochemical and Biophysical Research Communications, 526(2): 341−348. doi: 10.1016/j.bbrc.2020.03.092
    [65]
    Zhang Y, Wei C, Zhang PF, Li X, Liu T, Pu Y, et al. 2014. Efficient reprogramming of naïve-like induced pluripotent stem cells from porcine adipose-derived stem cells with a feeder-independent and serum-free system. PLoS One, 9(1): e85089. doi: 10.1371/journal.pone.0085089
    [66]
    Zhao H, Li YY, Wiriyahdamrong T, Yuan ZM, Qing YB, Li HH, et al. 2020. Improved production of GTKO/hCD55/hCD59 triple-gene-modified Diannan miniature pigs for xenotransplantation by recloning. Transgenic Research, 29(3): 369−379. doi: 10.1007/s11248-020-00201-2
    [67]
    Zhu ZS, Wu XL, Li Q, Zhang JQ, Yu S, Shen QY, et al. 2021. Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to define a pluripotency gene regulatory network. The FASEB Journal, 35(6): e21664.
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