Utf1, or Undifferentiated embryonic cell transcription factor 1, is a proline-rich, nuclear protein. It is highly conserved among placental mammals and plays essential roles in proper cell differentiation in pluripotent and germ cells. In the context of pluripotency, it aids in establishing a favorable chromatin state in embryonic stem cells, reducing “transcriptional noise” [1].

In Utf1 null mouse models, proper embryo development almost entirely depends on the presence of functional Utf1 alleles in the parental germline, indicating a link between its proposed epigenetic role in ESC pluripotency in vitro and intergenerational epigenetic inheritance in vivo [2]. In human iPSCs, Utf1 knockout significantly reduces reprogramming efficiency and increases spontaneous differentiation, highlighting its importance in maintaining iPSC identity and stability [3]. In P19 embryonal carcinoma cells, UTF1-deficient clones show higher neuron-differentiating potentials, suggesting that endogenous UTF1 prevents these cells from neuronal differentiation [4]. In stallions, UTF1 is expressed in undifferentiated spermatogonia and can be a putative marker for spermatogonial stem cells [5].

In conclusion, Utf1 is crucial for germ cell development, spermatogenesis, and maintaining male fertility in mice. It also plays a vital role in the generation and maintenance of pluripotent stem cells. The gene knockout studies in mouse models have revealed its significance in embryonic development, pluripotency, and differentiation, providing insights into its potential roles in related diseases and stem-cell-based therapies [1,2,3,4,5].

References:

1. Raina, Khyati, Dey, Chandrima, Thool, Madhuri, Sudhagar, S, Thummer, Rajkumar P. 2021. An Insight into the Role of UTF1 in Development, Stem Cells, and Cancer. In Stem cell reviews and reports, 17, 1280-1293. doi:10.1007/s12015-021-10127-9. https://pubmed.ncbi.nlm.nih.gov/33517544/

2. Bao, Qiuye, Morshedi, Amir, Wang, Fulu, Yu, Wei-Ping, Dröge, Peter. 2017. Utf1 contributes to intergenerational epigenetic inheritance of pluripotency. In Scientific reports, 7, 14612. doi:10.1038/s41598-017-14426-5. https://pubmed.ncbi.nlm.nih.gov/29097685/

3. Raina, Khyati, Modak, Kirti, Premkumar, Chitra, Velayudhan, Shaji R, Thummer, Rajkumar P. 2025. UTF1 Expression is Important for the Generation and Maintenance of Human iPSCs. In Stem cell reviews and reports, 21, 859-871. doi:10.1007/s12015-024-10836-x. https://pubmed.ncbi.nlm.nih.gov/39754619/

4. Lin, Chia-Hua, Yang, Chi-Hwa, Chen, Yi-Rong. 2011. UTF1 deficiency promotes retinoic acid-induced neuronal differentiation in P19 embryonal carcinoma cells. In The international journal of biochemistry & cell biology, 44, 350-7. doi:10.1016/j.biocel.2011.11.008. https://pubmed.ncbi.nlm.nih.gov/22107969/

5. Jung, Heejun, Roser, Janet F, Yoon, Minjung. 2014. UTF1, a putative marker for spermatogonial stem cells in stallions. In PloS one, 9, e108825. doi:10.1371/journal.pone.0108825. https://pubmed.ncbi.nlm.nih.gov/25272017/