- [Nature aging] Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche
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- 2025-05-29 13:51:38|
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- 2025-05-29 13:51:38|
[Title]
Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche in liver
[Corresponding Author]
Jong-Eun Park (jp24@kaist.ac.kr)
Chuna Kim (kimchuna@kribb.re.kr)
Nature Aging volume 5, pages929–949 (2025)
[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 specifc traits and diversity of these cells in aged tissues, along with their efects 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 fbrotic 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 profled 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 fbrotic niche. Finally, FiNi–ATAC-seq revealed age-associated epigenetic changes enriched in fbrotic niche cells. Thus, our quasi-spatial, single-cell profling method allows the detailed analysis of initial aging microenvironments, providing potential therapeutic targets for aging prevention.
Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche in liver
[Corresponding Author]
Jong-Eun Park (jp24@kaist.ac.kr)
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
- BioMedical Research Center, KAIST, Daejeon, Republic of Korea
Chuna Kim (kimchuna@kribb.re.kr)
- Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
- Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea
[Journal]
Nature Aging volume 5, pages929–949 (2025)[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 specifc traits and diversity of these cells in aged tissues, along with their efects 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 fbrotic 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 profled 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 fbrotic niche. Finally, FiNi–ATAC-seq revealed age-associated epigenetic changes enriched in fbrotic niche cells. Thus, our quasi-spatial, single-cell profling method allows the detailed analysis of initial aging microenvironments, providing potential therapeutic targets for aging prevention.