Skip to main content

Advertisement

SpringerLink
Log in

An Insight into the Role of UTF1 in Development, Stem Cells, and Cancer

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

The curiosity to understand the mechanisms regulating transcription in pluripotent cells resulted in identifying a unique transcription factor named Undifferentiated embryonic cell transcription factor 1 (UTF1). This proline-rich, nuclear protein is highly conserved among placental mammals with prominent expression observed in pluripotent, germ, and cancer cells. In pluripotent and germ cells, its role has been implicated primarily in proper cell differentiation, whereas in cancer, it shows tissue-specific function, either as an oncogene or a tumor suppressor gene. Furthermore, UTF1 is crucial for germ cell development, spermatogenesis, and maintaining male fertility in mice. In addition, recent studies have demonstrated the importance of UTF1 in the generation of high quality induced Pluripotent Stem Cells (iPSCs) and as an excellent biomarker to identify bona fide iPSCs. Functionally, UTF1 aids in establishing a favorable chromatin state in embryonic stem cells, reducing “transcriptional noise” and possibly functions similarly in re-establishing this state in differentiated cells upon their reprogramming to generate mature iPSCs. This review highlights the multifaceted roles of UTF1 and its implication in development, spermatogenesis, stem, and cancer cells.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

References

  1. Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.

    Article  CAS  PubMed  Google Scholar 

  2. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    Article  CAS  PubMed  Google Scholar 

  3. Okuda, A., Fukushima, A., Nishimoto, M., Orimo, A., Yamagishi, T., Nabeshima, Y., et al. (1998). UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells. The EMBO Journal, 17(7), 2019–2032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kristensen, D. M., Nielsen, J. E., Skakkebaek, N. E., Graem, N., Jacobsen, G. K., Rajpert-De Meyts, E., & Leffers, H. (2008). Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms. Human Reproduction (Oxford, England), 23(4), 775–782.

    Article  CAS  Google Scholar 

  5. Mouallif, M., Albert, A., Zeddou, M., Ennaji, M. M., Delvenne, P., & Guenin, S. (2014). Expression profile of undifferentiated cell transcription factor 1 in normal and cancerous human epithelia. International Journal of Experimental Pathology, 95(4), 251–259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fukushima, A., Okuda, A., Nishimoto, M., Seki, N., Hori, T., & Muramatsu, M. (1998). Characterization of functional domains of an embryonic stem cell coactivator UTF1 which are conserved and essential for potentiation of ATF-2 activity. Journal of Biological Chemistry, 273(40), 25840–25849.

    Article  CAS  PubMed  Google Scholar 

  7. Nishimoto, M., Katano, M., Yamagishi, T., Hishida, T., Kamon, M., Suzuki, A., et al. (2013). In Vivo Function and Evolution of the Eutherian-Specific Pluripotency Marker UTF1. PLOS ONE, 8(7), e68119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nishimoto, M., Fukushima, A., Miyagi, S., Suzuki, Y., Sugano, S., Matsuda, Y., et al. (2001). Structural analyses of the UTF1 gene encoding a transcriptional coactivator expressed in pluripotent embryonic stem cells. Biochemical and biophysical Research Communications, 285(4), 945–953.

    Article  CAS  PubMed  Google Scholar 

  9. Kooistra, S. M., Thummer, R. P., & Eggen, B. J. L. (2009). Characterization of human UTF1, a chromatin-associated protein with repressor activity expressed in pluripotent cells. Stem Cell Research, 2(3), 211–218.

    Article  CAS  PubMed  Google Scholar 

  10. Rodda, D. J., Chew, J.-L., Lim, L.-H., Loh, Y.-H., Wang, B., Ng, H.-H., & Robson, P. (2005). Transcriptional regulation of nanog by OCT4 and SOX2. Journal of Biological Chemistry, 280(26), 24731–24737.

    Article  CAS  PubMed  Google Scholar 

  11. Tan, S. M., Wang, S. T., Hentze, H., & Dröge, P. (2007). A UTF1-based selection system for stable homogeneously pluripotent human embryonic stem cell cultures. Nucleic Acids Research, 35(18), e118.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Nishimoto, M., Miyagi, S., Yamagishi, T., Sakaguchi, T., Niwa, H., Muramatsu, M., & Okuda, A. (2005). Oct-3/4 Maintains the Proliferative Embryonic Stem Cell State via Specific Binding to a Variant Octamer Sequence in the Regulatory Region of the UTF1 Locus. Molecular and Cellular Biology, 25(12), 5084–5094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nishimoto, M., Fukushima, A., Okuda, A., & Muramatsu, M. (1999). The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2. Molecular and Cellular Biology, 19(8), 5453–5465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. van den Boom, V., Kooistra, S. M., Boesjes, M., Geverts, B., Houtsmuller, A. B., Monzen, K., et al. (2007). UTF1 is a chromatin-associated protein involved in ES cell differentiation. The Journal of Cell Biology, 178(6), 913–924.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Thummer, R. P., Drenth-Diephuis, L. J., & Eggen, B. J. L. (2012). Constitutive GFP-UTF1 expression interferes with ES and EC cell differentiation. The Journal of Stem Cell Research and Therapy, 2(127), 1–7.

    Google Scholar 

  16. Thummer, R. P., Drenth-Diephuis, L. J., Carney, K. E., & Eggen, B. J. L. (2010). Functional characterization of single-nucleotide polymorphisms in the human undifferentiated embryonic-cell transcription factor 1 gene. DNA and Cell Biology, 29(5), 241–248.

    Article  CAS  PubMed  Google Scholar 

  17. Williamson, A. J. K., Smith, D. L., Blinco, D., Unwin, R. D., Pearson, S., Wilson, C., et al. (2008). Quantitative proteomics analysis demonstrates post-transcriptional regulation of embryonic stem cell differentiation to hematopoiesis. Molecular & Cellular Proteomics, 7(3), 459–472.

    Article  CAS  Google Scholar 

  18. Van Hoof, D., Muñoz, J., Braam, S. R., Pinkse, M. W. H., Linding, R., Heck, A. J. R., et al. (2009). Phosphorylation dynamics during early differentiation of human embryonic stem cells. Cell Stem Cell, 5(2), 214–226.

    Article  PubMed  CAS  Google Scholar 

  19. Hong, J., Kim, H., Park, C., Son, M., Lee, K. W., & Kim, Y. J. (2015). Identification of Undifferentiated Embryonic Cell Transcription Factor 1 as a Potential Substrate of Carboxyl-Terminal Domain Small Phosphatases. Journal of the Korean Chemical Society, 59(2), 188–193.

    Article  CAS  Google Scholar 

  20. Galonska, C., Smith, Z. D., & Meissner, A. (2014). In Vivo and in vitro dynamics of undifferentiated embryonic cell transcription factor 1. Stem Cell Reports, 2(3), 245–252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bao, Q., Morshedi, A., Wang, F., Bhargy, S., Pervushin, K., Yu, W.-P., & Dröge, P. (2017). UTF1 contributes to intergenerational epigenetic inheritance of pluripotency. Scientific Reports, 7(1), 1–11.

    Article  CAS  Google Scholar 

  22. Kasowitz, S. D., Luo, M., Ma, J., Leu, N. A., & Wang, P. J. (2017). Embryonic lethality and defective male germ cell development in mice lacking UTF1. Scientific Reports, 7(1), 1–10.

    Article  CAS  Google Scholar 

  23. de Sousa Lopes, S. M. C., van den Driesche, S., Carvalho, R. L. C., Larsson, J., Eggen, B., Surani, M. A., & Mummery, C. L. (2005). Altered primordial germ cell migration in the absence of transforming growth factor β signaling via ALK5. Developmental Biology, 284(1), 194–203.

    Article  CAS  Google Scholar 

  24. Nishimoto, M., Miyagi, S., Katayanagi, T., Tomioka, M., Muramatsu, M., & Okuda, A. (2003). The embryonic Octamer factor 3/4 displays distinct DNA binding specificity from those of other Octamer factors. Biochemical and Biophysical Research Communications, 302(3), 581–586.

    Article  CAS  PubMed  Google Scholar 

  25. Ivanova, N., Dobrin, R., Lu, R., Kotenko, I., Levorse, J., DeCoste, C., et al. (2006). Dissecting self-renewal in stem cells with RNA interference. Nature, 442(7102), 533.

    Article  CAS  PubMed  Google Scholar 

  26. Kooistra, S. M., van den Boom, V., Thummer, R. P., Johannes, F., Wardenaar, R., Tesson, B. M., et al. (2010). Undifferentiated embryonic cell transcription factor 1 regulates ESC chromatin organization and gene expression. Stem Cells, 28(10), 1703–1714.

    Article  CAS  PubMed  Google Scholar 

  27. Jia, J., Zheng, X., Hu, G., Cui, K., Zhang, J., Zhang, A., et al. (2012). Regulation of pluripotency and self-renewal of ESCs through epigenetic-threshold modulation and mRNA pruning. Cell, 151(3), 576–589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fukushima, A., Nishimoto, M., Okuda, A., & Muramatsu, M. (1999). Carboxy-terminally truncated form of a coactivator UTF1 stimulates transcription from a variety of gene promoters through the TATA Box. Biochemical and Biophysical Research Communications, 258(3), 519–523.

    Article  CAS  PubMed  Google Scholar 

  29. Zwaka, T. P. (2006). Keeping the noise down in ES cells. Cell, 127(7), 1301–1302.

    Article  CAS  PubMed  Google Scholar 

  30. Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., et al. (2006). A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 125(2), 315–326.

    Article  CAS  PubMed  Google Scholar 

  31. Laskowski, A. I., & Knoepfler, P. S. (2013). Myc binds the pluripotency factor Utf1 through the basic-helix-loop-helix leucine zipper domain. Biochemical and Biophysical Research Communications, 435(4), 551–556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Takahashi, K., & Yamanaka, S. (2006). Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell, 126(4), 663–676.

    Article  CAS  PubMed  Google Scholar 

  33. Zhao, Y., Yin, X., Qin, H., Zhu, F., Liu, H., Yang, W., et al. (2008). Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell, 3(5), 475–479.

    Article  CAS  PubMed  Google Scholar 

  34. Yang, C.-S., Chang, K.-Y., & Rana, T. M. (2014). Genome-wide functional analysis reveals factors needed at the transition steps of induced reprogramming. Cell Reports, 8(2), 327–337.

    Article  CAS  PubMed  Google Scholar 

  35. Schwarz, B. A., Cetinbas, M., Clement, K., Walsh, R. M., Cheloufi, S., Gu, H., et al. (2018). Prospective isolation of poised iPSC intermediates reveals principles of cellular reprogramming. Cell Stem Cell, 23(2), 289–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Buganim, Y., Faddah, D. A., Cheng, A. W., Itskovich, E., Markoulaki, S., Ganz, K., et al. (2012). Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell, 150(6), 1209–1222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Buganim, Y., Faddah, D. A., & Jaenisch, R. (2013). Mechanisms and models of somatic cell reprogramming. Nature Reviews Genetics, 14(6), 427–439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mikkelsen, T. S., Hanna, J., Zhang, X., Ku, M., Wernig, M., Schorderet, P., et al. (2008). Dissecting direct reprogramming through integrative genomic analysis. Nature, 454(7200), 49–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Graumann, J., Hubner, N. C., Kim, J. B., Ko, K., Moser, M., Kumar, C., et al. (2008). Stable isotope labeling by amino acids in cell culture (SILAC) and proteome quantitation of mouse embryonic stem cells to a depth of 5,111 proteins. Molecular & Cellular Proteomics, 7(4), 672–683.

    Article  CAS  Google Scholar 

  40. Lin, C.-H., Yang, C.-H., & Chen, Y.-R. (2012). UTF1 deficiency promotes retinoic acid-induced neuronal differentiation in P19 embryonal carcinoma cells. The international Journal of Biochemistry & Cell Biology, 44(2), 350–357.

    Article  CAS  Google Scholar 

  41. Wong, J. C. Y., Jack, M. M., Li, Y., & O’Neill, C. (2014). The epigenetic bivalency of core pancreatic β-cell transcription factor genes within mouse pluripotent embryonic stem cells is not affected by knockdown of the polycomb repressive complex 2, SUZ12. PLOS ONE, 9(5), e97820.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Morshedi, A., Noghabi, M. S., & Dröge, P. (2013). Use of UTF1 genetic control elements as iPSC reporter. Stem Cell Reviews and Reports, 9(4), 523–530.

    Article  CAS  PubMed  Google Scholar 

  43. Pfannkuche, K., Fatima, A., Gupta, M. K., Dieterich, R., & Hescheler, J. (2010). Initial colony morphology-based selection for iPS cells derived from adult fibroblasts is substantially improved by temporary UTF1-based selection. PlOS ONE, 5(3), e9580.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Semmler, J., Lehmann, M., Pfannkuche, K., Reppel, M., Hescheler, J., & Nguemo, F. (2014). Functional expression and regulation of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in mouse iPS cell-derived cardiomyocytes after UTF1-neo selection. Cellular Physiology and Biochemistry, 34(4), 1199–1215.

    Article  CAS  PubMed  Google Scholar 

  45. de Kretser, D. M., Loveland, K. L., Meinhardt, A., Simorangkir, D., & Wreford, N. (1998). Spermatogenesis. Human Reproduction, 13(suppl_1), 1–8.

    Article  PubMed  Google Scholar 

  46. Waheeb, R., & Hofmann, M. (2011). Human spermatogonial stem cells: a possible origin for spermatocytic seminoma. International Journal of Andrology, 34(4pt2), e296–e305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhou, W., Shao, H., Zhang, D., Dong, J., Cheng, W., Wang, L., et al. (2015). PTEN signaling is required for the maintenance of spermatogonial stem cells in mouse, by regulating the expressions of PLZF and UTF1. Cell & Bioscience, 5(1), 42.

    Article  CAS  Google Scholar 

  48. Ehmcke, J., Wistuba, J., & Schlatt, S. (2006). Spermatogonial stem cells: questions, models and perspectives. Human Reproduction Update, 12(3), 275–282.

    Article  CAS  PubMed  Google Scholar 

  49. Phillips, B. T., Gassei, K., & Orwig, K. E. (2010). Spermatogonial stem cell regulation and spermatogenesis. Philosophical Transactions of the Royal Society B: Biological Sciences, 365(1546), 1663–1678.

    Article  CAS  Google Scholar 

  50. De Rooij, D. G., & Griswold, M. D. (2012). Questions about spermatogonia posed and answered since 2000. Journal of Andrology, 33(6), 1085–1095.

    Article  PubMed  CAS  Google Scholar 

  51. Fayomi, A. P., & Orwig, K. E. (2018). Spermatogonial stem cells and spermatogenesis in mice, monkeys and men. Stem Cell Research, 29, 207–214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ehmcke, J., & Schlatt, S. (2006). A revised model for spermatogonial expansion in man: lessons from non-human primates. Reproduction, 132(5), 673–680.

    Article  CAS  PubMed  Google Scholar 

  53. Hu, K., Li, L., Liao, Y., & Liang, M. (2018). LncRNA Gm2044 highly expresses in spermatocyte and inhibits Utf1 translation by interacting with Utf1 mRNA. Genes & Genomics, 40(7), 781–787.

    Article  CAS  Google Scholar 

  54. van Bragt, M. P. A., Roepers-Gajadien, H. L., Korver, C. M., Bogerd, J., Okuda, A., Eggen, B. J. L., et al. (2008). Expression of the pluripotency marker UTF1 is restricted to a subpopulation of early A spermatogonia in rat testis. Reproduction, 136(1), 33–40.

    Article  PubMed  CAS  Google Scholar 

  55. Tang, W. W. C., Dietmann, S., Irie, N., Leitch, H. G., Floros, V. I., Bradshaw, C. R., et al. (2015). A unique gene regulatory network resets the human germline epigenome for development. Cell, 161(6), 1453–1467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Schwarzer, C., Siatkowski, M., Pfeiffer, M. J., Baeumer, N., Drexler, H. C., Wang, B., et al. (2014). Maternal age effect on mouse oocytes: new biological insight from proteomic analysis. Reproduction, 148(1), 55–72.

    Article  CAS  PubMed  Google Scholar 

  57. Neuhaus, N., Yoon, J., Terwort, N., Kliesch, S., Seggewiss, J., Huge, A., et al. (2017). Single-cell gene expression analysis reveals diversity among human spermatogonia. MHR: Basic Science of Reproductive Medicine, 23(2), 79–90.

    CAS  PubMed  Google Scholar 

  58. Lee, W.-Y., Lee, K.-H., Heo, Y.-T., Kim, N.-H., Kim, J.-H., Kim, J.-H., et al. (2014). Transcriptional coactivator undifferentiated embryonic cell transcription factor 1 expressed in spermatogonial stem cells: a putative marker of boar spermatogonia. Animal Reproduction Science, 150(3–4), 115–124.

    Article  CAS  PubMed  Google Scholar 

  59. Jung, H., Roser, J. F., & Yoon, M. (2014). UTF1, a putative marker for spermatogonial stem cells in stallions. PLOS ONE, 9(10), e108825.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Lee, Y. S., Jung, H. J., & Yoon, M. J. (2017). Undifferentiated embryonic cell transcription factor 1 (UTF 1) and deleted in azoospermia-like (DAZL) expression in the testes of donkeys. Reproduction in Domestic Animals, 52(2), 264–269.

    Article  CAS  PubMed  Google Scholar 

  61. Sharma, S., Schlatt, S., Van Pelt, A., & Neuhaus, N. (2019). Characterization and population dynamics of germ cells in adult macaque testicular cultures. PlOS ONE, 14(6), e0218194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. von Kopylow, K., Staege, H., Schulze, W., Will, H., & Kirchhoff, C. (2012). Fibroblast growth factor receptor 3 is highly expressed in rarely dividing human type A spermatogonia. Histochemistry and Cell Biology, 138(5), 759–772.

    Article  CAS  Google Scholar 

  63. Di Persio, S., Saracino, R., Fera, S., Muciaccia, B., Esposito, V., Boitani, C., et al. (2017). Spermatogonial kinetics in humans. Development, 144(19), 3430–3439.

    Article  PubMed  CAS  Google Scholar 

  64. Caldeira-Brant, A. L., Martinelli, L. M., Marques, M. M., Reis, A. B., Martello, R., Almeida, F., & Chiarini-Garcia, H. (2020). A subpopulation of human Adark spermatogonia behaves as the reserve stem cell. Reproduction, 159(4), 437–451.

    Article  CAS  PubMed  Google Scholar 

  65. Guan, K., Nayernia, K., Maier, L. S., Wagner, S., Dressel, R., Lee, J. H., et al. (2006). Pluripotency of spermatogonial stem cells from adult mouse testis. Nature, 440(7088), 1199–1203.

    Article  CAS  PubMed  Google Scholar 

  66. Tan, K., & Wilkinson, M. F. (2019). Human spermatogonial stem cells scrutinized under the single-cell magnifying glass. Cell Stem Cell, 24(2), 201–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Guo, J., Grow, E. J., Mlcochova, H., Maher, G. J., Lindskog, C., Nie, X., et al. (2018). The adult human testis transcriptional cell atlas. Cell Research, 28(12), 1141–1157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang, P., Li, J., Allan, R. W., Guo, C. C., Peng, Y., & Cao, D. (2010). Expression of UTF1 in primary and metastatic testicular germ cell tumors. American Journal of Clinical Pathology, 134(4), 604–612.

    Article  PubMed  Google Scholar 

  69. Liu, A., Cheng, L., Du, J., Peng, Y., Allan, R. W., Wei, L., et al. (2010). Diagnostic utility of novel stem cell markers SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in primary mediastinal germ cell tumors. The American Journal of Surgical Pathology, 34(5), 697–706.

    Article  PubMed  Google Scholar 

  70. Pantazis, G., Harter, P. N., Capper, D., Kohlhof, P., Mittelbronn, M., & Schittenhelm, J. (2014). The embryonic stem cell factor UTF1 serves as a reliable diagnostic marker for germinomas. Pathology, 46(3), 225–229.

    Article  CAS  PubMed  Google Scholar 

  71. Xu, C., Zhou, Y., & Chen, W. (2014). Expression of undifferentiated embryonic cell transcription factor-1 (UTF1) in breast cancers and their matched normal tissues. Cancer Cell International, 14(1), 116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Forte, A., Schettino, M. T., Finicelli, M., Cipollaro, M., Colacurci, N., Cobellis, L., & Galderisi, U. (2009). Expression pattern of stemness-related genes in human endometrial and endometriotic tissues. Molecular Medicine, 15(11–12), 392–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Guenin, S., Mouallif, M., Deplus, R., Lampe, X., Krusy, N., Calonne, E., et al. (2012). Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis. PlOS ONE, 7(8), e42704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wu, X.-L., & Zheng, P.-S. (2013). Undifferentiated embryonic cell transcription factor-1 (UTF1) inhibits the growth of cervical cancer cells by transactivating p27 Kip1. Carcinogenesis, 34(7), 1660–1668.

    Article  CAS  PubMed  Google Scholar 

  75. Melone, M. A. B., Giulano, M., Squillaro, T., Alessio, N., Casale, F., Mattioli, E., et al. (2009). Genes involved in regulation of stem cell properties: studies on their expression in a small cohort of neuroblastoma patients. Cancer Biology & Therapy, 8(13), 1300–1306.

    Article  CAS  Google Scholar 

  76. Cadenas, C., & Bolt, H. M. (2012). Estrogen receptors in human disease. Springer, 86, 1489–1490.

    CAS  Google Scholar 

  77. Deroo, B. J., & Korach, K. S. (2006). Estrogen receptors and human disease. The Journal of Clinical Investigation, 116(3), 561–570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Chung, S.-H., Franceschi, S., & Lambert, P. F. (2010). Estrogen and ERα: Culprits in cervical cancer? Trends in Endocrinology & Metabolism, 21(8), 504–511.

    Article  CAS  Google Scholar 

  79. Chik, F., Szyf, M., & Rabbani, S, A. (2011). Role of epigenetics in cancer initiation and progression. In Human Cell Transformation (pp. 91–104). Advances in Experimental Medicine and Biology, vol 720. New York: Springer.

  80. Sun, L., Chao, F., Luo, B., Ye, D., Zhao, J., Zhang, Q., et al. (2018). Impact of estrogen on the relationship between obesity and renal cell carcinoma risk in women. EBioMedicine, 34, 108–112.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Caiazza, F., Ryan, E. J., Doherty, G., Winter, D. C., & Sheahan, K. (2015). Estrogen receptors and their implications in colorectal carcinogenesis. Frontiers in Oncology, 5, 19.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674.

    Article  CAS  PubMed  Google Scholar 

  83. Bhat, S., Kabekkodu, S. P., Noronha, A., & Satyamoorthy, K. (2016). Biological implications and therapeutic significance of DNA methylation regulated genes in cervical cancer. Biochimie, 121, 298–311.

    Article  CAS  PubMed  Google Scholar 

  84. Nakagawa, T., Matsusaka, K., Misawa, K., Ota, S., Takane, K., Fukuyo, M., et al. (2017). Frequent promoter hypermethylation associated with human papillomavirus infection in pharyngeal cancer. Cancer Letters, 407, 21–31.

    Article  CAS  PubMed  Google Scholar 

  85. Eckhardt, F., Lewin, J., Cortese, R., Rakyan, V. K., Attwood, J., Burger, M., et al. (2006). DNA methylation profiling of human chromosomes 6, 20 and 22. Nature Genetics, 38(12), 1378–1385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Liang, X., Zhu, J., Li, Y., Xu, Y., Chen, K., Lv, L., & Mao, W. (2020). Treatment strategies for metastatic gastric cancer: chemotherapy, palliative surgery or radiotherapy? Future Oncology, 16(5), 91–102.

    Article  CAS  PubMed  Google Scholar 

  87. Organista-Nava, J., Gómez-Gómez, Y., & Gariglio, P. (2014). Embryonic stem cell-specific signature in cervical cancer. Tumor Biology, 35(3), 1727–1738.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all the members of the Laboratory for Stem Cell Engineering and Regenerative Medicine (SCERM) for their excellent support. This work was supported by North Eastern Region – Biotechnology Programme Management Cell (NERBPMC), Department of Biotechnology, Government of India (BT/PR16655/NER/95/132/2015), and also by IIT Guwahati Institutional Top-Up on Start-Up Grant.

Author information

Authors and Affiliations

  1. Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India

    Khyati Raina, Chandrima Dey, Madhuri Thool & Rajkumar P Thummer

  2. Department of Biotechnology, National Institute of Pharmaceutical Education and Research Guwahati, Changsari, Guwahati, Assam, 781101, India

    Madhuri Thool & S Sudhagar

Authors
  1. Khyati Raina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chandrima Dey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Madhuri Thool
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Sudhagar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rajkumar P Thummer
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the conception and design of this manuscript. Data collection and interpretation were performed by Khyati Raina, Chandrima Dey and Madhuri Thool. The first draft of the manuscript was written by Khyati Raina, Chandrima Dey and Madhuri Thool and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rajkumar P Thummer.

Ethics declarations

Competing Interests

The authors declare that they have no conflict of interest.

Ethics Approval

Not applicable

Informed Consent

Not applicable

Research Involving Human Participants and/or Animals

None.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raina, K., Dey, C., Thool, M. et al. An Insight into the Role of UTF1 in Development, Stem Cells, and Cancer. Stem Cell Rev and Rep 17, 1280–1293 (2021). https://doi.org/10.1007/s12015-021-10127-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-021-10127-9

Keywords

Search

Navigation