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JAK-STAT signaling regulation of chicken embryonic stem cell differentiation into male germ cells

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Abstract

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is crucial in chicken germ stem cell differentiation, but its role in the regulation of germ cell differentiation is unknown. To address this, cucurbitacin I or interleukin 6 was used to inhibit or activate JAK-STAT signaling during embryonic stem cells (ESCs) differentiation. The expression of downstream JAK-STAT signaling molecules was assessed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). PAS, and immunohistochemical staining of frozen sections was used to determine the appearance of primordial germ cells (PGCs) and, later, spermatogonial stem cells (SSCs) during gonadal development. Inhibition of the JAK-STAT signaling resulted in decreased expression of JAK2 and STAT3 as well as of PGCs markers; moreover, the proportion of CVH and C-KIT positive cells as well as the yield of PGCs were remarkably decreased, and the gonad was smaller than that of control samples. Conversely, activation of JAK-STAT resulted in increased expression of JAK2 and STAT3 as well as that of PGC marker CVH. In addition, the proportion of CVH and C-KIT-positive cells as well as the PGC yield was increased, and the gonad was significantly larger than that from control samples. Collectively, our results suggested that JAK-STAT effectively promoted the formation of PGCs in the genital ridge during early embryogenesis in vivo and played a positive role in the regulation of ESC to SSC differentiation in vitro, with JAK2 and STAT3 functioning as pivotal factors for intracellular signal transduction.

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References

  • Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296(5573):1653–1655

    Article  CAS  PubMed  Google Scholar 

  • Alghasham AA (2013) Cucurbitacins—a promising target for cancer therapy. International journal of health sciences 7(1):77–89

    Article  PubMed  PubMed Central  Google Scholar 

  • Arbouzova NI, Zeidler MP (2006) JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions. Development 133(14):2605–2616

    Article  CAS  PubMed  Google Scholar 

  • Asano H, Aonuma M, Sanosaka T, Kohyama J, Namihira M, Nakashima K (2009) Astrocyte differentiation of neural precursor cells is enhanced by retinoic acid through a change in epigenetic modification. Stem Cells 27(11):2744–2752

    Article  CAS  PubMed  Google Scholar 

  • Bannister SC, Smith CA, Roeszler KN, Doran TJ, Sinclair AH, Tizard MLV (2011) Manipulation of estrogen synthesis alters MIR202*expression in embryonic chicken gonads. Biol Reprod 85(1):22–30

    Article  CAS  PubMed  Google Scholar 

  • Beebe K, Lee WC, Micchelli CA (2010) JAK/STAT signaling coordinates stem cell proliferation and multilineage differentiation in the Drosophila intestinal stem cell lineage. Dev Biol 338(1):28–37

    Article  CAS  PubMed  Google Scholar 

  • Blaskovich MA, Sun JZ, Cantor A, Turkson J, Jove R, Sebti SM (2003) Discovery of JSI-124 (Cucurbitacin I), a selective janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res 63(6):1270–1279

    CAS  PubMed  Google Scholar 

  • Bowles J, Koopman P (2007) Retinoic acid, meiosis and germ cell fate in mammals. Development 134(19):3401–3411

    Article  CAS  PubMed  Google Scholar 

  • Brady JJ, Li M, Suthram S, Jiang H, Wong WH, Blau HM (2013) Early role for IL-6 signalling during generation of induced pluripotent stem cells revealed by heterokaryon RNA-Seq. Nat Cell Biol 15(10):1244–U1272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown S, Zeidler MP, Hombria JECG (2006) JAK/STAT signalling in Drosophila controls cell motility during germ cell migration. Dev Dynam 235(4):958–966

    Article  CAS  Google Scholar 

  • Dong S, Tweardy DJ (2002) Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways. Blood 99(8):2637–2646

    Article  CAS  PubMed  Google Scholar 

  • Eyal-Giladi H, Kochav S (1976) From cleavage to primitive streak formation: a complementary normal table and a new look at the first stages of the development of the chick: I. General morphology. Dev Biol 49(2):321–337

    Article  CAS  PubMed  Google Scholar 

  • Greenhalgh CJ, Hilton DJ (2001) Negative regulation of cytokine signaling. J Leukoc Biol 70(3):348–356

    CAS  PubMed  Google Scholar 

  • Gregory L, Came PJ, Brown S (2008) Stem cell regulation by JAK/STAT signaling in Drosophila. Semin Cell Dev Biol 19(4):407–413

    Article  CAS  PubMed  Google Scholar 

  • Hao YX, **g H, Bi Q, Zhang JZ, Qin L, Yang PT (2014) Intra-amygdala microinfusion of IL-6 impairs the auditory fear conditioning of rats via JAK/STAT activation. Behav Brain Res 275:88–95

    Article  CAS  PubMed  Google Scholar 

  • He Z, Kokkinaki M, Dym M (2009) Signaling molecules and pathways regulating the fate of spermatogonial stem cells. Microsc Res Tech 72(8):586–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herrera F, Chen Q, Schubert D (2010) Synergistic effect of retinoic acid and cytokines on the regulation of glial fibrillary acidic protein expression. J Biol Chem 285(50):38915–38922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirano T, Ishihara K, Hibi M (2000) Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 19(21):2548–2556

    Article  CAS  PubMed  Google Scholar 

  • Hou SX, Zheng ZY, Chen X, Perrimon N (2002) The JAK/STAT pathway in model organisms: emerging roles in cell movement. Dev Cell 3(6):765–778

    Article  CAS  PubMed  Google Scholar 

  • Hudson QJ, Smith CA, Sinclair AH (2005) Aromatase inhibition reduces expression of FOXL2 in the embryonic chicken ovary. Dev Dynam 233(3):1052–1055

    Article  CAS  Google Scholar 

  • Jee SH, Chu CY, Chiu HC, Huang YL, Tsai WL, Liao YH, Kuo ML (2004) Interleukin-6 induced basic fibroblast growth factor-dependent angiogenesis in basal cell carcinoma cell line via JAK/STAT3 and P13-kinase/Akt pathways. J Investig Dermatol 123(6):1169–1175

    Article  CAS  PubMed  Google Scholar 

  • Jung JS, Kim DK, Park TS, Lee SD, Lim JM, Han JY (2005) Development of novel markers for the characterization of chicken primordial germ. Cells. Stem Cells 23(5):689–698

    Article  CAS  PubMed  Google Scholar 

  • Kawasaki H, Eckner R, Yao TP, Taira K, Chiu R, Livingston DM, Yokoyama KK (1998) Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation. Nature 393(6682):284–289

    Article  CAS  PubMed  Google Scholar 

  • Kiger AA, Jones DL, Schulz C, Rogers MB, Fuller MT (2001) Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue. Science 294(5551):2542–2545

    Article  CAS  PubMed  Google Scholar 

  • Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW (2002) Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285(1–2):1–24

    Article  CAS  PubMed  Google Scholar 

  • Levy O, Ruvinov E, Reem T, Granot Y, Cohen S (2010) Highly efficient osteogenic differentiation of human mesenchymal stem cells by eradication of STAT3 signaling. International Journal of Biochemistry & Cell Biology 42(11):1823–1830

    Article  CAS  Google Scholar 

  • Li B, Wang XY, Tian Z, **ao XJ, Xu Q, Wei CX, YF, Sun HC, Chen GH (2010) Directional differentiation of chicken spermatogonial stem cells in vitro. Cytotherapy 12(3):326–331

    Article  CAS  PubMed  Google Scholar 

  • Liongue C, Ward AC (2013) Evolution of the JAK-STAT pathway. Jak-Stat 2(1):e22756

    Article  PubMed  PubMed Central  Google Scholar 

  • Lutticken C, Wegenka UM, Yuan J, Buschmann J, Schindler C, Ziemiecki A, Harpur AG, Wilks AF, Yasukawa K, Taga T (1994) Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. Science (New York, NY) 263(5143):89–92

    Article  CAS  Google Scholar 

  • Magnusdottir E, Dietmann S, Murakami K, Gunesdogan U, Tang F, Bao S, Diamanti E, Lao K, Gottgens B, Azim SM (2013) A tripartite transcription factor network regulates primordial germ cell specification in mice. Nat Cell Biol 15(8):905–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mulholland DJ, Dedhar S, Coetzee GA, Nelson CC (2005) Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know? Endocr Rev 26(7):898–915

    Article  CAS  PubMed  Google Scholar 

  • Nakajima K, Yamanaka Y, Nakae K, Kojima H, Ichiba M, Kiuchi N, Kitaoka T, Fukada T, Hibi M, Hirano T (1996) A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO (European Molecular Biology Organization) Journal 15(14):3651–3658

    CAS  Google Scholar 

  • Nefedova Y, Nagaraj S, Rosenbauer A, Muro-Cacho C, Sebti SM, Gabrilovich DI (2005) Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the Janus-activated kinase 2/signal transducers and activators of transcription 3 pathway. Cancer Res 65(20):9525–9535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oatley JM, Brinster RL (2008) Regulation of Spermatogonial stem cell self-renewal in mammals. Annual Review of Cell & Developmental Biology 24(24):263–286

    Article  CAS  Google Scholar 

  • Oatley JM, Kaucher AV, Avarbock MR, Brinster RL (2010) Regulation of mouse Spermatogonial stem cell differentiation by STAT3 signaling. Biol Reprod 83(3):427–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Shea JJ, Gadina M, Schreiber RD (2002) Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell 109:S121–S131

    Article  PubMed  Google Scholar 

  • Rawlings JS, Rosler KM, Harrison DA (2004) The JAK/STAT signaling pathway. J Cell Sci 117(8):1281–1283

    Article  CAS  PubMed  Google Scholar 

  • Sheng XR, Posenau T, Gumulak-Smith JJ, Matunis E, Van Doren M, Wawersik M (2009) Jak-STAT regulation of male germline stem cell establishment during Drosophila embryogenesis. Dev Biol 334(2):335–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi Q-Q, Sun M, Zhang Z-T, Zhang Y-N, Elsayed AK, Zhang L, Huang X-M, Li B-C (2014) A screen of suitable inducers for germline differentiation of chicken embryonic stem cells. Anim Reprod Sci 147(1–2):74–85

    Article  CAS  PubMed  Google Scholar 

  • Singh SR, Liu W, Hou SX (2007) The adult Drosophila malpighian tubules are maintained by multipotent stem cells. Cell Stem Cell 1(2):191–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trenerry MK, Della Gatta PA, Cameron-Smith D (2011) JAK/STAT signaling and human in vitro myogenesis. BMC Physiol 11:6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tulina N, Matunis E (2001) Control of stem cell self-renewal in Drosophila spermatogenesis by JAK-STAT signaling. Science 294(5551):2546–2549

    Article  CAS  PubMed  Google Scholar 

  • Wawersik M, Milutinovich A, Casper AL, Matunis E, Williams B, Van Doren M (2005) Somatic control of germline sexual development is mediated by the JAK/STAT pathway. Nature 436(7050):563–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams JG (2000) STAT signalling in cell proliferation and in development. Curr Opin Genet Dev 10(5):503–507

    Article  CAS  PubMed  Google Scholar 

  • Yabuta Y, Kurimoto K, Ohinata Y, Seki Y, Saitou M (2006) Gene expression dynamics during germline specification in mice identified by quantitative single-cell gene expression profiling. Biol Reprod 75(5):705–716

    Article  CAS  PubMed  Google Scholar 

  • Yadav A, Kumar B, Datta J, Teknos TN, Kumar P (2011) IL-6 promotes head and neck tumor metastasis by inducing epithelial-Mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res 9(12):1658–1667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan C, Ghaffari M, Whitsett JA, Zeng X, Sever Z, Lin S (1998) Retinoic acid-receptor activation of SP-B gene transcription in respiratory epithelial cells. Am J Phys 275(2 Pt 1):L239–L246

    CAS  Google Scholar 

  • Yan C, Naltner A, Martin M, Naltner M, Fangman JM, Gurel O (2002) Transcriptional stimulation of the surfactant protein B gene by STAT3 in respiratory epithelial cells. J Biol Chem 277(13):10967–10972

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Lian XM, Cowen A, Xu H, Du H, Yan C (2004) Synergy between signal transducer and activator of transcription 3 and retinoic acid receptor-alpha in regulation of the surfactant protein B gene in the lung. Mol Endocrinol 18(6):1520–1532

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Yang H, Zhang Z, Shi Q, Wang D, Zheng M, Li B, Song J (2013a) Isolation of chicken embryonic stem cell and preparation of chicken chimeric model. Mol Biol Rep 40(3):2149–2156

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Lv XD, Jiang J, Zhang L, Zhao Y (2013b) Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis. Cell Res 23(4):573–576

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zuo Q, Liu Z, Li D, Tang B, **ao TR, Lian C, Wang Y, ** K, Wang Y, Zhang W, Li B (2015a) The induction effect of Am80 and TSA on ESC differentiation via regulation of Stra8 in chicken. PLoS One 10(11):e0140262

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Z, Elsayed AK, Shi Q, Zhang Y, Zuo Q, Li D, Lian C, Tang B, **ao T, Xu Q, Chang G, Chen G, Zhang L, Wang K, Wang Y, ** K, Wang Y, Song J, Cui H, Li B (2015b) Crucial genes and pathways in chicken germ stem cell differentiation. J Biol Chem 290(21):13605–13621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (31572390), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. Jiangsu Key Laboratory for Animal Genetic, Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, 88 South University Road, Yangzhou, Jiangsu, 225009, China

    Yu Zhang, Lei Zhang, Qisheng Zuo, Yinjie Wang, Yani Zhang, Qi Xu, Bichun Li & Guohong Chen

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  1. Yu Zhang
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  2. Lei Zhang
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Correspondence to Guohong Chen.

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Zhang, Y., Zhang, L., Zuo, Q. et al. JAK-STAT signaling regulation of chicken embryonic stem cell differentiation into male germ cells. In Vitro Cell.Dev.Biol.-Animal 53, 728–743 (2017). https://doi.org/10.1007/s11626-017-0167-9

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