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Nature Aging, May 05 2025, | https://doi.org/10.1038/s43587-025-00857-7 Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche in liver

Kwon Yong Tak ^1,9, Juyeon Kim^2,3,9, Myungsun Park ^1,9, Wooseok Kim ¹, Seoyeong Lee ¹, Narae Park ^4,5, Min Jeong Kim ¹, Ju-Bin Kang ², Yongjun Koh ¹, Hae Young Yang ¹, Min Kyu Yum ¹, Injune Kim ^1,6, Yong Ryoul Yang ^2,7, Won-Il Jeong ¹, Jinsung Yang ⁸, Cheolju Lee ⁴, Chuna Kim ^2,3,* & Jong-Eun Park ^1,6,*

¹Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
²Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
³Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea.
⁴Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, Republic of Korea.
⁵KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, Republic of Korea.
⁶BioMedical Research Center, KAIST, Daejeon, Republic of Korea.
⁷Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea.
⁸Department of Biochemistry and Convergence Medical Science, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
⁹These authors contributed equally: Kwon Yong Tak, Juyeon Kim, Myungsun Park.

^*Corresponding authors: correspondence to Chuna Kim or Jong-Eun Park

Abstract

Aging is associated with the accumulation of senescent cells, which are triggered by tissue injury response and often escape clearance by the immune system. The specific traits and diversity of these cells in aged tissues, along with their effects on the tissue microenvironment, remain largely unexplored. Despite the advances in single-cell and spatial omics technologies to understand complex tissue architecture, senescent cell populations are often neglected in general analysis pipelines due to their scarcity and the technical bias in current omics toolkits. Here we used the physical properties of tissue to enrich the age-associated fibrotic niche and subjected them to single-cell RNA sequencing and single-nuclei ATAC sequencing (ATAC-seq) analysis and named this method fibrotic niche enrichment sequencing (FiNi-seq). Fibrotic niche of the tissue was selectively enriched based on its resistance to enzymatic digestion, enabling quasi-spatial analysis. We profiled young and old livers of male mice using FiNi-seq, discovered Wif1- and Smoc1-producing mesenchymal cell populations showing senescent phenotypes, and investigated the early immune responses within this fibrotic niche. Finally, FiNi-ATAC-seq revealed age-associated epigenetic changes enriched in fibrotic niche cells. Thus, our quasi-spatial, single-cell profiling method allows the detailed analysis of initial aging microenvironments, providing potential therapeutic targets for aging prevention.

논문정보

형식Research article
게재일2025년 05월 (BRIC 등록일 2025-05-09)
연구진국내 연구진
분야 생명과학 > 노화/암생물학

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