美国贝勒医学院Bruno Di Stefano小组的最新研究揭示了生物分子凝聚物中的选择性RNA隔离指导细胞命运转变。2025年10月28日出版的《自然—生物技术》杂志发表了这项成果。

在这里，研究人员探讨了细胞命运如何受到RNA凝聚体的影响，特别是P体，它在转录后调节基因表达。该课题组分析了多种脊椎动物在不同发育背景下的生物分子凝聚物的转录组。他们的分析揭示了对编码细胞命运调节因子的未翻译RNA的保守的、细胞类型特异性的隔离。P体RNA的含量并不反映每种细胞类型中活跃的基因表达，而是在前一个发育阶段的翻译抑制转录物中富集。从机制上讲，P体的含量是由microRNAs控制的，并且可以通过干扰AGO2或聚腺苷化位点的图像而深刻地重塑。将这些见解应用于干细胞分化，该团队表明，操纵P体组装或microRNA活性可以指导幼稚的小鼠和人类多能干细胞走向全能性，或引导引物的人类胚胎细胞走向生殖细胞谱系。他们的发现将细胞命运的决定与脊椎动物的RNA凝聚体联系起来，并提供了一种控制细胞身份的方法。

据悉，控制干细胞分化是生物医学研究的长期目标。

附：英文原文

Title: Selective RNA sequestration in biomolecular condensates directs cell fate transitions

Author: Pessina, Patrizia, Nevo, Mika, Shi, Junchao, Kodali, Srikanth, Casas, Eduard, Cui, Yingzhi, Richards, Alicia L., Park, Emily J., Chen, Xi, Levin-Ferreyra, Florencia, Rivera Tostado, Alejandra, Stevenson, Erica, Krogan, Nevan J., Swaney, Danielle L., Ying, Qilong, Chen, Qi, Brumbaugh, Justin, Di Stefano, Bruno

Issue&Volume: 2025-10-28

Abstract: Controlling stem cell differentiation is a longstanding goal in biomedical research. Here we explore how cell fate is influenced by RNA condensates, specifically P-bodies, which modulate gene expression posttranscriptionally. We profiled the transcriptomes of biomolecular condensates in diverse developmental contexts spanning multiple vertebrate species. Our analyses revealed conserved, cell type-specific sequestration of untranslated RNAs encoding cell fate regulators. P-body RNA contents do not reflect active gene expression in each cell type but are enriched for translationally repressed transcripts characteristic of the preceding developmental stage. Mechanistically, P-body contents are controlled by microRNAs and can be profoundly reshaped by perturbing AGO2 or polyadenylation site usage. Applying these insights to stem cell differentiation, we show that manipulating P-body assembly or microRNA activity can direct naive mouse and human pluripotent stem cells toward totipotency or primed human embryonic cells toward the germ cell lineage. Our findings link cell fate decisions to RNA condensates across vertebrates and provide a means of controlling cell identity.

DOI: 10.1038/s41587-025-02853-z

Source: https://www.nature.com/articles/s41587-025-02853-z