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Short telomeres impede germ cell specification by upregulating MAPK and TGFβ signaling

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Abstract

Functional telomeres protect chromosome ends and play important roles in stem cell maintenance and differentiation. Short telomeres negatively impact germ cell development and can contribute to age-associated infertility. Moreover, telomere syndrome resulting from mutations of telomerase or telomere-associated genes exhibits short telomeres and reduced fertility. It remains elusive whether and how telomere lengths affect germ cell specification. We report that functional telomere is required for the coordinated germ cell and somatic cell fate decisions. Using telomerase gene Terc deficient mice as a model, we show that short telomeres restrain germ cell specification of epiblast cells but promote differentiation towards somatic lineage. Short telomeres increase chromatin accessibility to elevate TGFβ and MAPK/ERK signaling for somatic cell differentiation. Notably, elevated Fst expression in TGFβ pathway represses the BMP4-pSmad signaling pathway, thus reducing germ cell formation. Re-elongation of telomeres by targeted knock-in of Terc restores normal chromatin accessibility to suppress TGFβ and MAPK signaling, thereby facilitating germ cell formation. Taken together, our data reveal that functional telomeres are required for germ cell specification by repressing TGFβ and MAPK signaling.

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References

  • Aramaki, S., Hayashi, K., Kurimoto, K., Ohta, H., Yabuta, Y., Iwanari, H., Mochizuki, Y., Hamakubo, T., Kato, Y., Shirahige, K., et al. (2013). A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants. Dev Cell 27, 516–529.

    Article  CAS  PubMed  Google Scholar 

  • Aydos, S.E., Elhan, A.H., and Tükün, A. (2005). Is telomere length one of the determinants of reproductive life span? Arch Gynecol Obstet 272, 113–116.

    Article  PubMed  Google Scholar 

  • Barbosa, R., Acevedo, L.A., and Marmorstein, R. (2021). The MEK/ERK network as a therapeutic target in human cancer. Mol Cancer Res 19, 361–374.

    Article  CAS  PubMed  Google Scholar 

  • Blasco, M.A., Lee, H.W., Hande, M.P., Samper, E., Lansdorp, P.M., DePinho, R.A., and Greider, C.W. (1997). Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34.

    Article  CAS  PubMed  Google Scholar 

  • Bosman, E.A., Lawson, K.A., Debruyn, J., Beek, L., Francis, A., Schoonjans, L., Huylebroeck, D., and Zwijsen, A. (2006). Smad5 determines murine amnion fate through the control of bone morphogenetic protein expression and signalling levels. Development 133, 3399–3409.

    Article  CAS  PubMed  Google Scholar 

  • Buenrostro, J.D., Giresi, P.G., Zaba, L.C., Chang, H.Y., and Greenleaf, W.J. (2013). Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods 10, 1213–1218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cawthon, R.M. (2002). Telomere measurement by quantitative PCR. Nucl Acids Res 30, 47e–47.

    Article  Google Scholar 

  • Coucouvanis, E., and Martin, G.R. (1999). BMP signaling plays a role in visceral endoderm differentiation and cavitation in the early mouse embryo. Development 126, 535–546.

    Article  CAS  PubMed  Google Scholar 

  • Criqui, M., Qamra, A., Chu, T.W., Sharma, M., Tsao, J., Henry, D.A., Barsyte-Lovejoy, D., Arrowsmith, C.H., Winegarden, N., Lupien, M., et al. (2020). Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment. eLife 9, e47333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai, K., Xu, H., Ouyang, N., Li, Y., Yuan, P., Wang, L., Zhao, X., and Wang, W. (2019). Correlation of human telomerase reverse transcriptase single nucleotide polymorphisms with in vitro fertilisation outcomes. J Assist Reprod Genet 36, 517–527.

    Article  PubMed  Google Scholar 

  • Darmishonnejad, Z., Zarei-Kheirabadi, F., Tavalaee, M., Zarei-Kheirabadi, M., Zohrabi, D., and Nasr-Esfahani, M.H. (2020). Relationship between sperm telomere length and sperm quality in infertile men. Andrologia 52, e13546.

    Article  PubMed  Google Scholar 

  • Fainsod, A., Deißler, K., Yelin, R., Marom, K., Epstein, M., Pillemer, G., Steinbeisser, H., and Blum, M. (1997). The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4. Mech Dev 63, 39–50.

    Article  CAS  PubMed  Google Scholar 

  • Fujiwara, T., Dunn, N.R., and Hogan, B.L.M. (2001). Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse. Proc Natl Acad Sci USA 98, 13739–13744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grabole, N., Tischler, J., Hackett, J.A., Kim, S., Tang, F., Leitch, H.G., Magnúsdóttir, E., and Surani, M.A. (2013). Prdm14 promotes germline fate and naive pluripotency by repressing FGF signalling and DNA methylation. EMBO Rep 14, 629–637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo, Q., Kumar, T.R., Woodruff, T., Hadsell, L.A., DeMayo, F.J., and Matzuk, M.M. (1998). Overexpression of mouse follistatin causes reproductive defects in transgenic mice. Mol Endocrinol 12, 96–106.

    Article  CAS  PubMed  Google Scholar 

  • Hackett, J.A., Zylicz, J.J., and Surani, M.A. (2012). Parallel mechanisms of epigenetic reprogramming in the germline. Trends Genet 28, 164–174.

    Article  CAS  PubMed  Google Scholar 

  • Hajkova, P., Ancelin, K., Waldmann, T., Lacoste, N., Lange, U.C., Cesari, F., Lee, C., Almouzni, G., Schneider, R., and Surani, M.A. (2008). Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452, 877–881.

    Article  CAS  PubMed  Google Scholar 

  • Hayashi, K., Kobayashi, T., Umino, T., Goitsuka, R., Matsui, Y., and Kitamura, D. (2002). SMAD1 signaling is critical for initial commitment of germ cell lineage from mouse epiblast. Mech Dev 118, 99–109.

    Article  CAS  PubMed  Google Scholar 

  • Hayashi, K., Ogushi, S., Kurimoto, K., Shimamoto, S., Ohta, H., and Saitou, M. (2012). Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice. Science 338, 971–975.

    Article  CAS  PubMed  Google Scholar 

  • Hayashi, K., Ohta, H., Kurimoto, K., Aramaki, S., and Saitou, M. (2011). Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell 146, 519–532.

    Article  CAS  PubMed  Google Scholar 

  • Herrera, E., Samper, E., Martín-Caballero, J., Flores, J.M., Lee, H.W., and Blasco, M.A. (1999). Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J 18, 2950–2960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hochberg, Y., and Benjamini, Y. (1990). More powerful procedures for multiple significance testing. Statist Med 9, 811–818.

    Article  CAS  Google Scholar 

  • Horbelt, D., Denkis, A., and Knaus, P. (2012). A portrait of transforming growth factor β superfamily signalling: background matters. Int J Biochem Cell Biol 44, 469–474.

    Article  CAS  PubMed  Google Scholar 

  • Huang, J., Wang, F., Okuka, M., Liu, N., Ji, G., Ye, X., Zuo, B., Li, M., Liang, P., Ge, W.W., et al. (2011). Association of telomere length with authentic pluripotency of ES/iPS cells. Cell Res 21, 779–792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jia, S., Ren, Z., Li, X., Zheng, Y., and Meng, A. (2008). smad2 and smad3 are required for mesendoderm induction by transforming growth factor-β/nodal signals in zebrafish. J Biol Chem 283, 2418–2426.

    Article  CAS  PubMed  Google Scholar 

  • Kalmbach, K.H., Antunes, D.M.F., Kohlrausch, F., and Keefe, D.L. (2015). Telomeres and female reproductive aging. Semin Reprod Med 33, 389–395.

    Article  CAS  PubMed  Google Scholar 

  • Keefe, D.L., and Liu, L. (2009). Telomeres and reproductive aging. Reprod Fertil Dev 21, 10–14.

    Article  CAS  PubMed  Google Scholar 

  • Kimura, T., Kaga, Y., Ohta, H., Odamoto, M., Sekita, Y., Li, K., Yamano, N., Fujikawa, K., Isotani, A., Sasaki, N., et al. (2014). Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition. Stem Cells 32, 2668–2678.

    Article  CAS  PubMed  Google Scholar 

  • Kurimoto, K., Yabuta, Y., Hayashi, K., Ohta, H., Kiyonari, H., Mitani, T., Moritoki, Y., Kohri, K., Kimura, H., Yamamoto, T., et al. (2015). Quantitative dynamics of chromatin remodeling during germ cell specification from mouse embryonic stem cells. Cell Stem Cell 16, 517–532.

    Article  CAS  PubMed  Google Scholar 

  • Lawson, K.A., Dunn, N.R., Roelen, B.A.J., Zeinstra, L.M., Davis, A.M., Wright, C.V.E., Korving, J.P.W.F.M., and Hogan, B.L.M. (1999). Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 13, 424–436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, H.W., Blasco, M.A., Gottlieb, G.J., Horner II, J.W., Greider, C.W., and DePinho, R.A. (1998). Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569–574.

    Article  CAS  PubMed  Google Scholar 

  • Li, Z., Fei, T., Zhang, J., Zhu, G., Wang, L., Lu, D., Chi, X., Teng, Y., Hou, N., Yang, X., et al. (2012). BMP4 signaling acts via dual-specificity phosphatase 9 to control ERK activity in mouse embryonic stem cells. Cell Stem Cell 10, 171–182.

    Article  CAS  PubMed  Google Scholar 

  • Liu, L., Bailey, S.M., Okuka, M., Muñoz, P., Li, C., Zhou, L., Wu, C., Czerwiec, E., Sandler, L., Seyfang, A., et al. (2007). Telomere lengthening early in development. Nat Cell Biol 9, 1436–1441.

    Article  CAS  PubMed  Google Scholar 

  • Liu, L., Blasco, M.A., and Keefe, D.L. (2002). Requirement of functional telomeres for metaphase chromosome alignments and integrity of meiotic spindles. EMBO Rep 3, 230–234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, L., Franco, S., Spyropoulos, B., Moens, P.B., Blasco, M.A., and Keefe, D.L. (2004). Irregular telomeres impair meiotic synapsis and recombination in mice. Proc Natl Acad Sci USA 101, 6496–6501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, N., Yin, Y., Wang, H., Zhou, Z., Sheng, X., Fu, H., Guo, R., Wang, H., Yang, J., Gong, P., et al. (2019). Telomere dysfunction impairs epidermal stem cell specification and differentiation by disrupting BMP/pSmad/P63 signaling. PLoS Genet 15, e1008368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • M’kacher, R., Colicchio, B., Marquet, V., Borie, C., Najar, W., Hempel, W. M., Heidingsfelder, L., Oudrhiri, N., Al Jawhari, M., Wilhelm-Murer, N., et al. (2021). Telomere aberrations, including telomere loss, doublets, and extreme shortening, are increased in patients with infertility. Fertil Steril 115, 164–173.

    Article  PubMed  Google Scholar 

  • Magnúsdóttir, E., Dietmann, S., Murakami, K., Günesdogan, U., Tang, F., Bao, S., Diamanti, E., Lao, K., Gottgens, B., and Azim Surani, M. (2013). A tripartite transcription factor network regulates primordial germ cell specification in mice. Nat Cell Biol 15, 905–915.

    Article  PubMed  PubMed Central  Google Scholar 

  • Magnúsdóttir, E., and Surani, M.A. (2014). How to make a primordial germ cell. Development 141, 245–252.

    Article  PubMed  Google Scholar 

  • Mangaonkar, A.A., and Patnaik, M.M. (2018). Short telomere syndromes in clinical practice: bridging bench and bedside. Mayo Clinic Proc 93, 904–916.

    Article  Google Scholar 

  • Mansour, A.A.F., Gafni, O., Weinberger, L., Zviran, A., Ayyash, M., Rais, Y., Krupalnik, V., Zerbib, M., Amann-Zalcenstein, D., Maza, I., et al. (2012). The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming. Nature 488, 409–413.

    Article  CAS  PubMed  Google Scholar 

  • Martínez, P., and Blasco, M.A. (2011). Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer 11, 161–176.

    Article  PubMed  Google Scholar 

  • Miyauchi, H., Ohta, H., Nagaoka, S., Nakaki, F., Sasaki, K., Hayashi, K., Yabuta, Y., Nakamura, T., Yamamoto, T., and Saitou, M. (2017). Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice. EMBO J 36, 3100–3119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgani, S.M., and Hadjantonakis, A.K. (2021). Quantitative analysis of signaling responses during mouse primordial germ cell specification. Biol Open 10.

  • Nakaki, F., Hayashi, K., Ohta, H., Kurimoto, K., Yabuta, Y., and Saitou, M. (2013). Induction of mouse germ-cell fate by transcription factors in vitro. Nature 501, 222–226.

    Article  CAS  PubMed  Google Scholar 

  • Ohinata, Y., Ohta, H., Shigeta, M., Yamanaka, K., Wakayama, T., and Saitou, M. (2009). A signaling principle for the specification of the germ cell lineage in mice. Cell 137, 571–584.

    Article  CAS  PubMed  Google Scholar 

  • Ohinata, Y., Payer, B., O’Carroll, D., Ancelin, K., Ono, Y., Sano, M., Barton, S.C., Obukhanych, T., Nussenzweig, M., Tarakhovsky, A., et al. (2005). Blimp1 is a critical determinant of the germ cell lineage in mice. Nature 436, 207–213.

    Article  CAS  PubMed  Google Scholar 

  • Picelli, S., Björklund, A.K., Reinius, B., Sagasser, S., Winberg, G., and Sandberg, R. (2014a). Tn5 transposase and tagmentation procedures for massively scaled sequencing projects. Genome Res 24, 2033–2040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Picelli, S., Faridani, O.R., Björklund, A.K., Winberg, G., Sagasser, S., and Sandberg, R. (2014b). Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc 9, 171–181.

    Article  CAS  PubMed  Google Scholar 

  • Plath, K., Fang, J., Mlynarczyk-Evans, S.K., Cao, R., Worringer, K.A., Wang, H., de la Cruz, C.C., Otte, A.P., Panning, B., and Zhang, Y. (2003). Role of histone H3 lysine 27 methylation in X inactivation. Science 300, 131–135.

    Article  CAS  PubMed  Google Scholar 

  • Poon, S.S.S., Martens, U.M., Ward, R.K., and Lansdorp, P.M. (1999). Telomere length measurements using digital fluorescence microscopy. Cytometry 36, 267–278.

    Article  CAS  PubMed  Google Scholar 

  • Reig-Viader, R., Garcia-Caldés, M., and Ruiz-Herrera, A. (2016). Telomere homeostasis in mammalian germ cells: a review. Chromosoma 125, 337–351.

    Article  CAS  PubMed  Google Scholar 

  • Reik, W., and Surani, M.A. (2015). Germline and pluripotent stem cells. Cold Spring Harb Perspect Biol 7, a019422.

    Article  PubMed  PubMed Central  Google Scholar 

  • Robinson, L.R.G. Jr, Pimentel, R., Wang, F., Kramer, Y.G., Gonullu, D.C., Agarwal, S., Navarro, P.A., McCulloh, D., and Keefe, D.L. (2020). Impaired reproductive function and fertility preservation in a woman with a dyskeratosis congenita. J Assist Reprod Genet 37, 1221–1225.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rudolph, K.L., Chang, S., Lee, H.W., Blasco, M., Gottlieb, G.J., Greider, C., and DePinho, R.A. (1999). Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701–712.

    Article  CAS  PubMed  Google Scholar 

  • Saitou, M. (2009). Specification of the germ cell lineage in mice. Front Biosci 14, 1068–1087.

    Article  CAS  Google Scholar 

  • Saitou, M., and Miyauchi, H. (2016). Gametogenesis from pluripotent stem cells. Cell Stem Cell 18, 721–735.

    Article  CAS  PubMed  Google Scholar 

  • Savage, S.A., and Bertuch, A.A. (2010). The genetics and clinical manifestations of telomere biology disorders. Genet Med 12, 753–764.

    Article  PubMed  Google Scholar 

  • Schoeftner, S., Blanco, R., Lopez de Silanes, I., Muñoz, P., Gómez-López, G., Flores, J.M., and Blasco, M.A. (2009). Telomere shortening relaxes X chromosome inactivation and forces global transcriptome alterations. Proc Natl Acad Sci USA 106, 19393–19398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seisenberger, S., Andrews, S., Krueger, F., Arand, J., Walter, J., Santos, F., Popp, C., Thienpont, B., Dean, W., and Reik, W. (2012). The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 48, 849–862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaul, Y.D., and Seger, R. (2007). The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim Biophys Acta (BBA)-Mol Cell Res 1773, 1213–1226.

    Article  CAS  Google Scholar 

  • Sun, Y., Liu, W.Z., Liu, T., Feng, X., Yang, N., and Zhou, H.F. (2015). Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Receptors Signal Transduction 35, 600–604.

    Article  CAS  Google Scholar 

  • Tian, C., Liu, L., Ye, X., Fu, H., Sheng, X., Wang, L., Wang, H., Heng, D., and Liu, L. (2019). Functional oocytes derived from granulosa cells. Cell Rep 29, 4256–4267.e9.

    Article  CAS  PubMed  Google Scholar 

  • Uysal, F., Kosebent, E.G., Toru, H.S., and Ozturk, S. (2021). Decreased expression of TERT and telomeric proteins as human ovaries age may cause telomere shortening. J Assist Reprod Genet 38, 429–441.

    Article  PubMed  Google Scholar 

  • Vasilopoulos, E., Fragkiadaki, P., Kalliora, C., Fragou, D., Docea, A.O., Vakonaki, E., Tsoukalas, D., Calina, D., Buga, A.M., Georgiadis, G., et al. (2019). The association of female and male infertility with telomere length (Review). Int J Mol Med 44, 375–389.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, P., Miao, Y., Li, X.H., Zhang, N., Wang, Q., Yue, W., Sun, S.C., Xiong, B., Qiao, J., and Li, M. (2021). Proteome landscape and spatial map of mouse primordial germ cells. Sci China Life Sci 64, 966–981.

    Article  CAS  PubMed  Google Scholar 

  • Wen, L., Liu, Q., Xu, J., Liu, X., Shi, C., Yang, Z., Zhang, Y., Xu, H., Liu, J., Yang, H., et al. (2020). Recent advances in mammalian reproductive biology. Sci China Life Sci 63, 18–58.

    Article  PubMed  Google Scholar 

  • Wu, J., Huang, B., Chen, H., Yin, Q., Liu, Y., Xiang, Y., Zhang, B., Liu, B., Wang, Q., Xia, W., et al. (2016). The landscape of accessible chromatin in mammalian preimplantation embryos. Nature 534, 652–657.

    Article  CAS  PubMed  Google Scholar 

  • Wu, Q., Fukuda, K., Weinstein, M., Graff, J.M., and Saga, Y. (2015). SMAD2 and p38 signaling pathways act in concert to determine XY primordial germ cell fate in mice. Development 142, 575–586.

    Article  CAS  PubMed  Google Scholar 

  • Ying, Y., Liu, X.M., Marble, A., Lawson, K.A., and Zhao, G.Q. (2000). Requirement of Bmp8b for the generation of primordial germ cells in the mouse. Mol Endocrinol 14, 1053–1063.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, J., Zhang, M., Acampora, D., Vojtek, M., Yuan, D., Simeone, A., and Chambers, I. (2018a). OTX2 restricts entry to the mouse germline. Nature 562, 595–599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, M., Leitch, H.G., Tang, W.W.C., Festuccia, N., Hall-Ponsele, E., Nichols, J., Surani, M.A., Smith, A., and Chambers, I. (2018b). Esrrb complementation rescues development of nanog-null germ cells. Cell Rep 22, 332–339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y., Feng, X.H., Wu, R.Y., and Derynck, R. (1996). Receptor-associated Mad homologues synergize as effectors of the TGF-β response. Nature 383, 168–172.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by China National Key R&D Program (2018YFA0107002, 2018YFC1003004) and the National Natural Science Foundation of China (32030033, 31430052). We thank Huasong Wang and Jie Li from Nankai University for assisting the experiments and discussion, and Haoze Vincent Yu from University of California San Diego for providing Tn5 enzyme and assisting the sample preparation of ATAC-seq.

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Authors and Affiliations

  1. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China

    Chenglei Tian, Dai Heng, Nannan Zhao, Linlin Liu, Xiaoyan Sheng, Jiyu Chen & Lin Liu

  2. Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Chenglei Tian, Nannan Zhao & Lin Liu

  3. Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, 300071, China

    Dai Heng, Nannan Zhao, Linlin Liu, Jiyu Chen & Lin Liu

  4. Institute of Translational Medicine, Tianjin Union Medical Center, Nankai University, Tianjin, 300000, China

    Chenglei Tian & Lin Liu

  5. The Danish Stem Cell Center, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen N, Denmark

    Chenglei Tian

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Tian, C., Heng, D., Zhao, N. et al. Short telomeres impede germ cell specification by upregulating MAPK and TGFβ signaling. Sci. China Life Sci. 66, 324–339 (2023). https://doi.org/10.1007/s11427-022-2151-0

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