Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2023-01-12 , DOI: 10.1007/s12015-023-10504-6 Yuchen Sun 1 , Xinglin Hu 1 , Dan Qiu 1 , Zhijing Zhang 1 , Lei Lei 1
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As the first and rate-limiting step in ribosome biogenesis, rDNA transcription undergoes significant dynamic changes during cell pluripotency alteration. Over the past decades, rDNA activity has demonstrated dynamic changes, but most people view it as passive compliance with cellular needs. The evidence for rDNA transcriptional activity determining stem cell pluripotency is growing as research advances, resulting in the arrest of embryonic development and impairment of stem cell lines stemness by rDNA transcription inhibition. The exact mechanism by which rDNA activation influences pluripotency remains unknown. The first objective of this opinion article is to describe rDNA changes in the pathological and physiological course of life, including developmental diseases, tumor genesis, and stem cell differentiation. After that, we propose three hypotheses regarding rDNA regulation of pluripotency: 1) Specialized ribosomes synthesized from rDNA variant, 2) Nucleolar stress induced by the drop of rDNA transcription, 3) Interchromosomal interactions between rDNA and other genes. The pluripotency regulatory center is expected to focus strongly on rDNA. A small molecule inhibitor of rDNA is used to treat tumors caused by abnormal pluripotency activation. By understanding how rDNA regulates pluripotency, we hope to treat developmental diseases and safely apply somatic cell reprogramming in clinical settings.
Graphical Abstract
中文翻译：
发育性疾病和干细胞中的 rDNA 转录
作为核糖体生物发生的第一步和限速步骤，rDNA 转录在细胞多能性改变过程中经历显着的动态变化。在过去的几十年里，rDNA 活动表现出动态变化，但大多数人认为它是被动地顺应细胞需求。随着研究的进展，rDNA 转录活性决定干细胞多能性的证据越来越多，导致 rDNA 转录抑制导致胚胎发育停滞和干细胞系干性受损。rDNA 激活影响多能性的确切机制仍然未知。这篇观点文章的第一个目标是描述 rDNA 在生命病理和生理过程中的变化，包括发育疾病、肿瘤发生和干细胞分化。在那之后，我们提出了关于 rDNA 多能性调节的三个假设：1）由 rDNA 变体合成的特化核糖体，2）由 rDNA 转录下降引起的核仁应激，3）rDNA 与其他基因之间的染色体间相互作用。多能性监管中心预计将重点关注 rDNA。rDNA 的小分子抑制剂用于治疗由异常多能性激活引起的肿瘤。通过了解 rDNA 如何调节多能性，我们希望治疗发育性疾病并在临床环境中安全地应用体细胞重编程。多能性监管中心预计将重点关注 rDNA。rDNA 的小分子抑制剂用于治疗由异常多能性激活引起的肿瘤。通过了解 rDNA 如何调节多能性，我们希望治疗发育性疾病并在临床环境中安全地应用体细胞重编程。多能性监管中心预计将重点关注 rDNA。rDNA 的小分子抑制剂用于治疗由异常多能性激活引起的肿瘤。通过了解 rDNA 如何调节多能性，我们希望治疗发育性疾病并在临床环境中安全地应用体细胞重编程。
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