AbstractThe transcription factors NANOG and POU5F1 (OCT4) play crucial roles in maintaining pluripotency in embryonic stem (ES) cells. While their functions have been well-studied, the specific interactions between NANOG and POU5F1 and their combined effects on pluripotency in ES-like and Epiblast cells remain less understood.

摘要转录因子NANOG和POU5F1（OCT4）在维持胚胎干（ES）细胞的多能性中起着至关重要的作用。虽然它们的功能已经得到了很好的研究，但NANOG和POU5F1之间的特定相互作用及其对ES样和外胚层细胞多能性的综合影响仍然不太清楚。

Understanding these associations is vital for refining pluripotent stem cell characterization and advancing regenerative medicine. In this matter, we investigated the associations between NANOG and POU5F1 in maintaining pluripotency in ES-like and Epiblast cells and how these interactions contribute to the distinct pluripotent states of these cells.

了解这些关联对于完善多能干细胞表征和推进再生医学至关重要。在这方面，我们研究了NANOG和POU5F1在维持ES样细胞和外胚层细胞多能性方面的关联，以及这些相互作用如何促成这些细胞的不同多能状态。

In the present paper, we examined the pattern of NANOG expression by the immunocytochemical method in embryonic stem-like (ES-like) cells and compared it with its expression pattern in embryonic stem cells (ESCs). Similarly, we examined the expression pattern of POU5F1 in ES-like cells, ESCs, and epiblast cells and compared the expression pattern of these two genes with each other.

在本文中，我们通过免疫细胞化学方法检测了NANOG在胚胎干细胞样（ES样）细胞中的表达模式，并将其与胚胎干细胞（ESC）中的表达模式进行了比较。同样，我们检查了POU5F1在ES样细胞，ESC和外胚层细胞中的表达模式，并比较了这两个基因的表达模式。

On the other hand, using Fluidigm Biomark system analysis, we compared the amount of NANOG mRNA in these three cell lines and differentiated and undifferentiated Spermatogonial stem cells in several passages. Microscopic observations indicated the cytoplasmic expression of NANOG in the considered cells; moreover, they showed a similar expression pattern of NANOG with POU5F1 in the experimented cells.

另一方面，使用Fluidigm Biomark系统分析，我们比较了这三种细胞系中NANOG mRNA的量以及几代分化和未分化的精原干细胞。显微镜观察表明NANOG在所考虑的细胞中的细胞质表达；此外，他们在实验细胞中显示出与POU5F1相似的NANOG表达模式。

It has also been suggested that the more limited the cell’s pluripotency, the lower the expression of these two genes. However, the decrease in NANOG expression is less than that of POU5F1. Fluidigm real-time RT-PCR analysis also confirmed these results. During the experimental process, protein-protein (PPI) network analysis sho.

也有人提出，细胞的多能性越有限，这两个基因的表达就越低。然而，NANOG表达的降低小于POU5F1的降低。Fluidigm实时RT-PCR分析也证实了这些结果。在实验过程中，蛋白质-蛋白质（PPI）网络分析显示。

IntroductionPluripotency, the ability of a cell to differentiate into any cell type within an organism, is a fundamental property of embryonic stem (ES) cells1,2. This characteristic is governed by a complex network of transcription factors, among which NANOG and POU5F1 (OCT4) play pivotal roles3. NANOG is known for its critical function in maintaining the undifferentiated state of ES cells, while POU5F1 is essential for the self-renewal and pluripotency of these cells4.

。这一特征受转录因子的复杂网络控制，其中NANOG和POU5F1（OCT4）起着关键作用3。NANOG以其维持ES细胞未分化状态的关键功能而闻名，而POU5F1对于这些细胞的自我更新和多能性至关重要4。

Despite extensive studies on their individual contributions, the precise nature of their interactions and the combined effects on pluripotency across different stem cell types remain incompletely understood5,6.Recent advances in stem cell biology have revealed that pluripotency is not a uniform state but a spectrum, with subtle differences in molecular signatures depending on the cell type and developmental stage7,8.

尽管对它们的个体贡献进行了广泛的研究，但它们相互作用的确切性质以及对不同干细胞类型多能性的综合影响仍未完全了解5,6。干细胞生物学的最新进展表明，多能性不是一种统一的状态，而是一种光谱，分子特征的细微差异取决于细胞类型和发育阶段7,8。

For instance, ES cells derived from the blastocyst’s inner cell mass (ICM) represent a “naive” pluripotent state characterized by a specific transcriptional profile and high levels of NANOG and POU5F17,9. In contrast, epiblast cells, which emerge slightly later in development, exhibit a “primed” pluripotent state with distinct molecular characteristics, reflecting their readiness for lineage commitment10,11.Given these disparities, it is essential to understand how NANOG and POU5F1 interact within and between these pluripotent states12.

例如，源自胚泡内细胞团（ICM）的ES细胞代表“幼稚”多能状态，其特征在于特定的转录谱和高水平的NANOG和POU5F17,9。相比之下，发育稍晚的外胚层细胞表现出具有不同分子特征的“引发”多能状态，反映了它们对谱系承诺的准备10,11。鉴于这些差异，了解NANOG和POU5F1如何在这些多能状态内和之间相互作用是至关重要的12。

This understanding could provide insight into the underlying mechanisms that govern the transition from a naive to a primed state and the maintenance of pluripotency itself13. Furthermore, elucidating these interactions could have significant implications for regenerative medicine, where precise modulation of the pluripotent state of stem cells is crucial fo.

这种理解可以深入了解控制从幼稚状态过渡到引发状态以及维持多能性本身的潜在机制13。此外，阐明这些相互作用可能对再生医学产生重大影响，其中干细胞多能状态的精确调节对于再生医学至关重要。

Data availability

数据可用性

The data sets analyzed for the current study are available from the corresponding author on reasonable request.

本研究分析的数据集可根据合理要求从通讯作者处获得。

AbbreviationsSSC:

缩写SSC：

Spermatogonial Stem Cell

精原干细胞

ESC:

电子稳定控制系统：

Embryonic Stem Cells

胚胎干细胞

ICM:

ICM公司：

Inner Cell Mass

内部细胞团

mESC:

mESC：

mutant EmbryonicStem Cell

突变胚胎干细胞

PGC:

PGC公司：

Primordial Germ Cell

原始生殖细胞

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Download referencesAcknowledgementsThis research was supported by the biotechnology faculty of Amol University of Special Modern Technologies, Islamic Republic of Iran, and the University of Heidelberg, Institute for Anatomy and Cell Biology III, Department of Neuroanatomy, Germany.FundingThis work was supported by the Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.Author informationAuthors and AffiliationsFaculty of Biotechnology, Amol University of Special Modern Technologies, P.O.Box: 46168-49767, Amol, IranMehdi Mehdinezhad Roshan, Hossein Azizi & Kiana SojoudiDepartment of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranMehdi Mehdinezhad RoshanAuthorsMehdi Mehdinezhad RoshanView author publicationsYou can also search for this author in.

下载参考文献致谢本研究得到了伊朗伊斯兰共和国阿莫尔特殊现代技术大学生物技术学院和德国海德堡大学神经解剖学系解剖与细胞生物学研究所III的支持。资助这项工作得到了德国海德堡大学医学院解剖与细胞生物学研究所的支持。作者信息作者和所属机构阿莫尔特殊现代技术大学生物技术学院，邮政信箱：46168-49767，阿莫尔，IranMehdi Mehdinezhad Roshan，Hossein Azizi＆Kiana SojoudieDepartment of Reproductive Biology，Faculty of Advanced Medical Sciences，大不里士医科大学，大不里士，IranMehdi Mehdinezhad RoshanAuthorsMehdi Mehdinezhad RoshanView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarHossein AziziView author publicationsYou can also search for this author in

PubMed Google ScholarHossein AziziView作者出版物您也可以在

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PubMed Google ScholarContributionsMMR: Carried out the experiment, assembly of data and data analysis, wrote the manuscript and edited the final document; HA: Carried out and designed the experiment; KS: data analysis; the authors read and approved the final manuscript.Corresponding authorCorrespondence to.

PubMed Google ScholarContributionsMMR：进行了实验，数据组装和数据分析，撰写了手稿并编辑了最终文件；HA：进行并设计了实验；KS：数据分析；作者阅读并批准了最终稿件。对应作者对应。

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The animal experiments were approved by the ethical committee of Amol University of Special Modern Technologies (It.ausmt.rec.1400.04). All methods were carried out following relevant guidelines and regulations. Also, all methods are reported according to the ARRIVE guidelines.

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Reprints and permissionsAbout this articleCite this articleRoshan, M.M., Azizi, H. & Sojoudi, K. A novel investigation of NANOG and POU5F1 associations in the pluripotent characterization of ES-like and epiblast cells.

转载和许可本文引用本文Roshan，M.M.，Azizi，H。＆Sojoudi，K。一项关于ES样和外胚层细胞多能表征中NANOG和POU5F1关联的新研究。

Sci Rep 14, 24092 (2024). https://doi.org/10.1038/s41598-024-75529-4Download citationReceived: 19 February 2024Accepted: 07 October 2024Published: 15 October 2024DOI: https://doi.org/10.1038/s41598-024-75529-4Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1424092（2024）。https://doi.org/10.1038/s41598-024-75529-4Download引文收到日期：2024年2月19日接受日期：2024年10月7日发布日期：2024年10月15日OI：https://doi.org/10.1038/s41598-024-75529-4Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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KeywordsNANOGPOU5F1ES-like cellsEpiblast cellsSpermatogenesisPPI network

关键词NANOGPOU5F1ES样细胞成核细胞精子发生PPI网络