Chromatin landscape dynamics during reprogramming towards human naïve and primed pluripotency reveals the divergent function of PRDM1 isoforms.

IF 6.1 2区生物学 Q1 CELL BIOLOGY Cell Death Discovery Pub Date : 2024-11-19 DOI:10.1038/s41420-024-02230-w

Jianfeng Zhou, Mingyue Guo, Guang Yang, Xinyu Cui, Jindian Hu, Tan Lin, Hong Wang, Shaorong Gao, Cizhong Jiang, Liping Wang, Yixuan Wang

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Abstract

Induced pluripotent stem cells (iPSCs) technology holds great potential in both scientific research and clinical applications. It enables the generation of naïve and primed iPSCs from various cell types through different strategies. Despite extensive characterizations of transcriptional and epigenetic factors, the intricacies of chromatin landscape dynamics during naïve and primed reprogramming, particularly in humans, remain poorly understood. In this study, we employed ATAC-seq and RNA-seq analyses to delineate and compare the chromatin landscape of naïve and primed pluripotency through the human secondary reprogramming system. Our investigations revealed several key transcriptional and epigenetic factors pivotal for reprogramming-associated chromatin remodeling. Notably, we found two isoforms of PRDM1, PRDM1α, and PRDM1β, bind to distinct genomic loci and play different roles in the naïve reprogramming process. We proposed an auto-regulatory model explaining the distinct functions of PRDM1α and PRDM1β. Overall, our findings highlight the complexity and diversity of transcription factors in shaping chromatin landscape dynamics and directing the fates of pluripotent cells.

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人类原始多能性和原始多能性重编程过程中的染色质景观动态揭示了 PRDM1 同工型的不同功能。

诱导多能干细胞（iPSCs）技术在科学研究和临床应用方面都具有巨大潜力。它能通过不同的策略，从各种细胞类型中生成幼稚和原始的 iPSCs。尽管对转录和表观遗传因子进行了广泛表征，但人们对原始和初始重编程过程中染色质景观动态的复杂性仍然知之甚少，尤其是在人类中。在本研究中，我们采用 ATAC-seq 和 RNA-seq 分析方法，通过人类二次重编程系统，描述并比较了幼稚多能性和原始多能性的染色质景观。我们的研究揭示了重编程相关染色质重塑的几个关键转录和表观遗传因子。值得注意的是，我们发现PRDM1的两种异构体PRDM1α和PRDM1β与不同的基因组位点结合，并在幼稚重编程过程中发挥不同的作用。我们提出了一个自动调节模型来解释 PRDM1α 和 PRDM1β 的不同功能。总之，我们的研究结果凸显了转录因子在塑造染色质景观动态和引导多能细胞命运方面的复杂性和多样性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.