2023-11-09 マックス・プランク研究所
◆門脈周辺の細胞は脂肪の代謝に特化し、酸素が少ない領域では炭水化物が分解される。老化においては、どの遺伝子が活性化され、細胞の代謝が変化し、エピジェネティックな変化が起こるかが注目されました。
◆これにより、老化研究では細胞の位置と種類に注目する必要があります。研究は、単一細胞レベルで異なるデータを組み合わせることで新たな代謝プロセスの理解が可能となり、バイオインフォマティクスが洞察を提供しています。
<関連情報>
- https://www.mpg.de/21085057/1109-balt-location-location-location-155436-x
- https://www.nature.com/articles/s43587-023-00513-y
老化マウス肝臓のメタボローム、トランスクリプトーム、エピゲノムの空間および単一細胞プロファイリング Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver
Chrysa Nikopoulou,Niklas Kleinenkuhnen,Swati Parekh,Tonantzi Sandoval,Christoph Ziegenhain,Farina Schneider,Patrick Giavalisco,Kat-Folz Donahue,Anna Juliane Vesting,Marcel Kirchner,Mihaela Bozukova,Christian Vossen,Janine Altmüller,Thomas Wunderlich,Rickard Sandberg,Vangelis Kondylis,Achim Tresch & Peter Tessarz
Nature Aging Published:09 November 2023
DOI:https://doi.org/10.1038/s43587-023-00513-y
Abstract
Tissues within an organism and even cell types within a tissue can age with different velocities. However, it is unclear whether cells of one type experience different aging trajectories within a tissue depending on their spatial location. Here, we used spatial transcriptomics in combination with single-cell ATAC-seq and RNA-seq, lipidomics and functional assays to address how cells in the male murine liver are affected by age-related changes in the microenvironment. Integration of the datasets revealed zonation-specific and age-related changes in metabolic states, the epigenome and transcriptome. The epigenome changed in a zonation-dependent manner and functionally, periportal hepatocytes were characterized by decreased mitochondrial fitness, whereas pericentral hepatocytes accumulated large lipid droplets. Together, we provide evidence that changing microenvironments within a tissue exert strong influences on their resident cells that can shape epigenetic, metabolic and phenotypic outputs.
