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深入探讨 UTF1 在发育、干细胞和癌症中的作用。

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

机构信息

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

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

出版信息

Stem Cell Rev Rep. 2021 Aug;17(4):1280-1293. doi: 10.1007/s12015-021-10127-9. Epub 2021 Jan 30.

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.

摘要

对理解多能细胞中转录调控机制的好奇心导致鉴定出一种独特的转录因子,命名为未分化胚胎细胞转录因子 1(UTF1)。这种富含脯氨酸的核蛋白在胎盘哺乳动物中高度保守,在多能性、生殖细胞和癌细胞中表达明显。在多能性和生殖细胞中,其主要作用涉及细胞的正常分化,而在癌症中,它表现出组织特异性功能,既是癌基因又是抑癌基因。此外,UTF1 对生殖细胞发育、精子发生和维持雄性生育力至关重要。此外,最近的研究表明 UTF1 在高质量诱导多能干细胞(iPSC)的生成中具有重要作用,并且作为鉴定真正 iPSC 的优秀生物标志物。在功能上,UTF1 有助于在胚胎干细胞中建立有利的染色质状态,减少“转录噪声”,并且在将其重编程为生成成熟 iPSC 以使其分化细胞中重新建立这种状态时可能具有类似的功能。这篇综述强调了 UTF1 的多方面作用及其在发育、精子发生、干细胞和癌细胞中的意义。

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