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Effect of BMP–Wnt–Nodal signal on stem cell differentiation

Published online by Cambridge University Press:  28 June 2021

Liyun Wang Open the ORCID record for Liyun Wang [Opens in a new window] ,
Ronghua Ma ,
Gongxue Jia ,
Shengyan Jian ,
Xianghui Zeng ,
Zhengfang Xiong ,
Binye Li  and
Chen Li
Liyun Wang
Affiliation:
Guangzhou Huadu Maternal and Child Health Hospital, Guangzhou, Guangdong, China
Ronghua Ma
Affiliation:
Qinghai Provincial People’s Hospital, Xining, Qinghai, China
Gongxue Jia
Affiliation:
Northwest China institute of Plateau Biology, Xining, Qinghai, China
Shengyan Jian
Affiliation:
Qinghai Provincial People’s Hospital, Xining, Qinghai, China
Xianghui Zeng
Affiliation:
Qinghai Provincial People’s Hospital, Xining, Qinghai, China
Zhengfang Xiong*
Affiliation:
Qinghai Provincial People’s Hospital, Xining, Qinghai, China
Binye Li
Affiliation:
Qinghai Provincial People’s Hospital, Xining, Qinghai, China
Chen Li
Affiliation:
Qinghai Provincial People’s Hospital, Xining, Qinghai, China
*
*Author for correspondence: Zhengfang Xiong. Qinghai Provincial People’s Hospital, Xining, Qinghai, China. Email: [email protected]
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Summary

The generation of germ cells from embryonic stem cells in vitro has current historical significance. Western blot, qPCR, immunofluorescence and flow cytometry assays were used to investigate the differences in expression levels of totipotency and specific markers for Wnt regulation and the related signalling pathways during primordial germ cell-like cell (PGCLC) induction and differentiation. During PGCLC induction, activation of WNT3a increased the expression of NANOG, SOX2 and OCT4, but Mvh, DAZL, Blimp1, TFAP2C, Gata4, SOX17, EOMES, Brachyury and PRDM1 expression levels were significantly reduced. Inhibition of the WNT signal demonstrated the opposite effect. Similarly, inhibitors of BMP and the Nodal/Activin signal were used to determine the effect of signal pathways on differentiation. CER1 affected the Wnt signal and differentiation, but the inhibitor SB only regulated differentiation. BMP–WNT–NODAL were mainly responsible for regulating differentiation. Our results provide a reliable theoretical basis and feasibility for further clinical medical research.

Keywords

Bone morphogenetic proteinDifferentiationEmbryonic stem cellsNodal/ActivinWnt signalling pathway
Type
Research Article
Information
Zygote , Volume 30 , Issue 1 , February 2022 , pp. 138 - 143
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Bertacchi, M, Pandolfini, L, D’Onofrio, M, Brandi, R and Cremisi, F (2015). The double inhibition of endogenously produced BMP and Wnt factors synergistically triggers dorsal telencephalic differentiation of mouse ES cells. Dev Neurobiol 75, 66–79.CrossRefGoogle ScholarPubMed
Bogliotti, YS, Wu, J, Vilarino, M, Okamura, D, Soto, DA, Zhong, C, Sakurai, M, Sampaio, RV, Suzuki, K, Izpisua Belmonte, JC and Ross, PJ (2018). Efficient derivation of stable primed pluripotent embryonic stem cells from bovine blastocysts. Proc Natl Acad Sci USA 115, 2090–5.CrossRefGoogle ScholarPubMed
Bothun, AM and Woods, DC (2019). Dynamics of WNT signaling components in the human ovary from development to adulthood. Histochem Cell Biol 151, 115–23.CrossRefGoogle Scholar
Cantú, AV, Altshuler-Keylin, S and Laird, DJ (2016). Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling. J Cell Biol 214, 215–29.CrossRefGoogle ScholarPubMed
Chen, D, Liu, W, Lukianchikov, A, Hancock, GV, Zimmerman, J, Lowe, MG, Kim, R, Galic, Z, Irie, N, Surani, MA, Jacobsen, SE and Clark, AT (2017). Germline competency of human embryonic stem cells depends on eomesodermin. Biol Reprod 97, 850–61.CrossRefGoogle ScholarPubMed
Chen, J, Nefzger, CM, Rossello, FJ, Sun, YBY, Lim, SM, Liu, X, de Boer, S, Knaupp, AS, Li, J, Davidson, KC, Polo, JM and Barberi, T (2018). Fine tuning of canonical wnt stimulation enhances differentiation of pluripotent stem cells independent of β-catenin-mediated T-cell factor signaling. Stem Cells (Dayt Ohio) 36, 822–33.CrossRefGoogle ScholarPubMed
Cheng, T, Zhai, K, Chang, Y, Yao, G, He, J, Wang, F, Kong, H, Xin, H, Wang, H, Jin, M, Gong, B, Gu, L, Yang, Z, Wu, Y, Ji, G and Sun, Y (2017). CHIR99021 combined with retinoic acid promotes the differentiation of primordial germ cells from human embryonic stem cells. Oncotarget 8, 7814–26.CrossRefGoogle ScholarPubMed
Chhabra, S, Liu, L, Goh, R, Kong, X and Warmflash, A (2019). Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids. PLoS Biol 17, e3000498.CrossRefGoogle ScholarPubMed
Chi, L, Saarela, U, Railo, A, Prunskaite-Hyyryläinen, R, Skovorodkin, I, Anthony, S, Katsu, K, Liu, Y, Shan, J, Salgueiro, AM, Belo, JA, Davies, J, Yokouchi, Y and Vainio, SJ (2011). A secreted BMP antagonist, Cer1, fine tunes the spatial organization of the ureteric bud tree during mouse kidney development. PLoS One 6, e27676.CrossRefGoogle ScholarPubMed
Divisato, G, Passaro, F, Russo, T and Parisi, S (2020). The key role of microRNAs in self-renewal and differentiation of embryonic stem cells. Int J Mol Sci 21,.CrossRefGoogle Scholar
Eskandari, N, Hassani Moghaddam, M, Atlasi, MA, Amini Mahabadi, J, Taherian, A and Nikzad, H (2018). The combination of retinoic acid and estrogen can increase germ cells genes expression in mouse embryonic stem cells derived primordial germ cells. Biologicals 56, 39–44.CrossRefGoogle ScholarPubMed
Fei, T, Zhu, S, Xia, K, Zhang, J, Li, Z, Han, JD and Chen, YG (2010). Smad2 mediates activin/Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells. Cell Res 20, 1306–18.CrossRefGoogle ScholarPubMed
Hackett, JA, Huang, Y, Günesdogan, U, Gretarsson, KA, Kobayashi, T, Surani, MA (2018). Tracing the transitions from pluripotency to germ cell fate with CRISPR screening. Nat Commun 9, 4292.CrossRefGoogle ScholarPubMed
Hofsteen, P, Robitaille, AM, Strash, N, Palpant, N, Moon, RT, Pabon, L and Murry, CE (2018). ALPK2 promotes cardiogenesis in zebrafish and human pluripotent stem cells. iScience 2, 88–100.CrossRefGoogle ScholarPubMed
Jeon, K, Kumar, D, Conway, AE, Park, K, Jothi, R and Jetten, AM (2019). GLIS3 transcriptionally activates WNT genes to promote differentiation of human embryonic stem cells into posterior neural progenitors. Stem Cells (Dayt Ohio) 37, 202–15.CrossRefGoogle ScholarPubMed
Koel, M, Võsa, U, Krjutškov, K, Einarsdottir, E, Kere, J, Tapanainen, J, Katayama, S, Ingerpuu, S, Jaks, V, Stenman, UH, Lundin, K, Tuuri, T and Salumets, A (2017). Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-β/activin/nodal signalling inhibition. Reprod Biomed Online 35, 253–63.CrossRefGoogle ScholarPubMed
Kojima, Y, Sasaki, K, Yokobayashi, S, Sakai, Y, Nakamura, T, Yabuta, Y, Nakaki, F, Nagaoka, S, Woltjen, K, Hotta, A, Yamamoto, T and Saitou, M (2017). Evolutionarily distinctive transcriptional and signaling programs drive human germ cell lineage specification from pluripotent stem cells. Cell Stem Cell 21, 517–32.e5.CrossRefGoogle ScholarPubMed
Lee, KH, Li, M, Michalowski, AM, Zhang, X, Liao, H, Chen, L, Xu, Y, Wu, X and Huang, J (2010). A genomewide study identifies the Wnt signaling pathway as a major target of p53 in murine embryonic stem cells. Proc Natl Acad Sci U S A 107, 69–74.CrossRefGoogle ScholarPubMed
Mansouri, V, Salehi, M, Omrani, MD, Niknam, Z and Ardeshirylajimi, A (2017). Collagen-alginate microspheres as a 3D culture system for mouse embryonic stem cells differentiation to primordial germ cells. Biologicals 48, 114–20.CrossRefGoogle ScholarPubMed
Martyn, I, Kanno, TY, Ruzo, A, Siggia, ED and Brivanlou, AH (2018). Self-organization of a human organizer by combined Wnt and Nodal signalling. Nature 558, 132–5.CrossRefGoogle ScholarPubMed
Morizane, A, Doi, D, Kikuchi, T, Nishimura, K and Takahashi, J (2011). Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells. J Neurosci Res 89, 117–26.CrossRefGoogle ScholarPubMed
Mucksová, J, Reinišová, M, Kalina, J, Lejčková, B, Hejnar, J and Trefil, P (2019). Conservation of chicken male germline by orthotopic transplantation of primordial germ cells from genetically distant donors. Biol Reprod 101, 200–7.CrossRefGoogle Scholar
Oestrup, O, Hall, V, Petkov, SG, Wolf, XA, Hyldig, S and Hyttel, P (2009). From zygote to implantation: morphological and molecular dynamics during embryo development in the pig. Reprod Domest Anim 44(suppl 3), 39–49.CrossRefGoogle ScholarPubMed
Osei-Sarfo, K and Gudas, LJ (2014). Retinoic acid suppresses the canonical Wnt signaling pathway in embryonic stem cells and activates the noncanonical Wnt signaling pathway. Stem Cells (Dayt Ohio) 32, 2061–71.CrossRefGoogle ScholarPubMed
Price, FD, Yin, H, Jones, A, van Ijcken, W, Grosveld, F and Rudnicki, MA (2013). Canonical Wnt signaling induces a primitive endoderm metastable state in mouse embryonic stem cells. Stem Cells (Dayt Ohio) 31, 752–64.CrossRefGoogle Scholar
Senft, AD, Bikoff, EK, Robertson, EJ and Costello, I (2019). Genetic dissection of Nodal and Bmp signalling requirements during primordial germ cell development in mouse. Nat Commun 10, 1089.CrossRefGoogle Scholar
Sierra, RA, Hoverter, NP, Ramirez, RN, Vuong, LM, Mortazavi, A, Merrill, BJ, Waterman, ML and Donovan, PJ (2018). TCF7L1 suppresses primitive streak gene expression to support human embryonic stem cell pluripotency. Development 145, dev161075.CrossRefGoogle ScholarPubMed
Sudheer, S, Bhushan, R, Fauler, B, Lehrach, H and Adjaye, J (2012). FGF inhibition directs BMP4-mediated differentiation of human embryonic stem cells to syncytiotrophoblast. Stem Cells Dev 21, 2987–3000.CrossRefGoogle ScholarPubMed
Susman, MW, Karuna, EP, Kunz, RC, Gujral, TS, Cantú, AV, Choi, SS, Jong, BY, Okada, K, Scales, MK, Hum, J, Hu, LS, Kirschner, MW, Nishinakamura, R, Yamada, S, Laird, DJ, Jao, LE, Gygi, SP, Greenberg, ME and Ho, HH (2017). Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates. eLife. 6, e26509.CrossRefGoogle Scholar
Suzuki, H, Kanai-Azuma, M and Kanai, Y (2015). From sex determination to initial folliculogenesis in mammalian ovaries: morphogenetic waves along the anteroposterior and dorsoventral axes. Sex Dev 9, 190–204.CrossRefGoogle ScholarPubMed
Tabata, H, Hara, T and Kitajima, K (2019). Inhibitory action of an ERK1/2 inhibitor on primitive endoderm cell differentiation from mouse embryonic stem cells. Biochem Biophys Res Commun 512, 399–404.CrossRefGoogle ScholarPubMed
ten Berge, D, Kurek, D, Blauwkamp, T, Koole, W, Maas, A, Eroglu, E, Siu, RK and Nusse, R (2011). Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. Nat Cell Biol 13, 1070–5.CrossRefGoogle ScholarPubMed
Velasco-Tirado, V, Alonso-Sardón, M, Lopez-Bernus, A, Romero-Alegría, Á, Burguillo, FJ, Muro, A, Carpio-Pérez, A, Muñoz Bellido, JL, Pardo-Lledias, J, Cordero, M and Belhassen-García, M (2018). Medical treatment of cystic echinococcosis: systematic review and meta-analysis. BMC Infect Dis 18, 306.CrossRefGoogle ScholarPubMed
Wang, D, Wang, Y, Liu, H, Tong, C, Ying, Q, Sachinidis, A, Li, L and Peng, L (2019). Laminin promotes differentiation of rat embryonic stem cells into cardiomyocytes by activating the integrin/FAK/PI3K p85 pathway. J Cell Mol Med 23, 3629–40.CrossRefGoogle ScholarPubMed
Zhao, H, Li, M, Ouyang, Q, Lin, G and Hu, L (2020). VEGF promotes endothelial cell differentiation from human embryonic stem cells mainly through PKC-ε/η pathway. Stem Cells Dev 29, 90–9.CrossRefGoogle ScholarPubMed
Zhong, W, Lai, Y, Yu, T, Xia, ZS, Yuan, YH, Ouyang, H, Shan, TD and Chen, QK (2017). Wnt and Nodal signaling simultaneously induces definitive endoderm differentiation of mouse embryonic stem cells. Rom J Morphol Embryol 58, 527–35.Google ScholarPubMed
Zhu, J, Wang, Y, Yu, W, Xia, K, Huang, Y, Wang, J, Liu, B, Tao, H, Liang, C and Li, F (2019). Long noncoding RNA: function and mechanism on differentiation of mesenchymal stem cells and embryonic stem cells. Curr Stem Cell Res Ther 14, 259–67.CrossRefGoogle ScholarPubMed
Zuccarini, M, Giuliani, P, Ziberi, S, Carluccio, M, Iorio, PD, Caciagli, F and Ciccarelli, R (2018). The role of Wnt signal in glioblastoma development and progression: A possible new pharmacological target for the therapy of this tumor. Genes 9, 105.CrossRefGoogle ScholarPubMed