Rajachandran Shreya, Xu Qianlan, Cao Qiqi, Zhang Xin, Chen Fei, Mangiameli Sarah M, Chen Haiqi
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Commun. 2025 May 14;16(1):4457. doi: 10.1038/s41467-025-59801-3.
The subcellular localization of RNA is closely linked to its function. Many RNA species are partitioned into organelles and other subcellular compartments for storage, processing, translation, or degradation. Thus, capturing the subcellular spatial distribution of RNA would directly contribute to the understanding of RNA functions and regulation. Here, we present PHOTON, a method which combines high resolution imaging with high throughput sequencing to achieve spatial transcriptome profiling at subcellular resolution. We demonstrate PHOTON as a versatile tool to accurately capture the transcriptome of target cell types in situ at the tissue level such as granulosa cells in the ovary, as well as RNA content within subcellular compartments such as the nucleoli, the mitochondria, and the stress granules. Using PHOTON, we also reveal the functional role of mA modifications on mRNA partitioning into stress granules. These results collectively demonstrate that PHOTON is a flexible and generalizable platform for understanding subcellular molecular dynamics through the transcriptomic lens.
RNA的亚细胞定位与其功能密切相关。许多RNA种类被分隔到细胞器和其他亚细胞区室中进行储存、加工、翻译或降解。因此，捕获RNA的亚细胞空间分布将直接有助于理解RNA的功能和调控。在这里，我们介绍了PHOTON，这是一种将高分辨率成像与高通量测序相结合的方法，以实现亚细胞分辨率下的空间转录组分析。我们证明PHOTON是一种通用工具，能够在组织水平原位准确捕获靶细胞类型的转录组，如卵巢中的颗粒细胞，以及亚细胞区室（如核仁、线粒体和应激颗粒）内的RNA含量。利用PHOTON，我们还揭示了mRNA上的mA修饰对其分配到应激颗粒中的功能作用。这些结果共同表明，PHOTON是一个灵活且可推广的平台，用于通过转录组学视角理解亚细胞分子动力学。
