Core Viewpoint - The article discusses a recent study published in *Nature* by a team from ETH Zurich, which reveals that the transcriptional changes in fat cells during obesity persist even two years after successful weight loss, indicating a phenomenon referred to as "fat memory" [7][11][22]. Group 1: Research Findings - The study analyzed fat tissue samples from participants who underwent weight loss surgery, showing that many differentially expressed genes (DEGs) during obesity remained dysregulated two years post-weight loss [11][13]. - In mouse experiments, previously obese mice exhibited a significantly enhanced ability to absorb sugars and fats, leading to faster weight regain when re-exposed to a high-fat diet [8][24]. - The research found that the longer the duration of obesity, the poorer the recovery of gene expression post-weight loss, suggesting that "fat memory" is influenced by the duration of obesity [21][25]. Group 2: Cellular and Molecular Mechanisms - Single-nucleus RNA sequencing revealed that the composition of cell types in the fat tissue did not change significantly between the time points, but many obesity-related DEGs remained altered [13][20]. - The study highlighted that the transcriptional dysregulation was most pronounced in adipocytes, adipocyte progenitor cells, and endothelial cells, with downregulation of fat metabolism pathways and upregulation of fibrosis and apoptosis-related pathways [14][20]. - The findings suggest that epigenetic changes account for 57-62% of downregulated DEGs and 68-75% of upregulated DEGs, indicating that epigenetic mechanisms play a crucial role in "fat memory" [22].

Core Viewpoint - The article discusses the development of a novel spatial multi-omics technology, Spatial-DMT, which enables the simultaneous mapping of DNA methylation and gene expression at near single-cell resolution, enhancing the understanding of tissue biology and its implications in development and disease [2][5][7]. Group 1: Technology Development - The research team from the University of Pennsylvania developed Spatial-DMT, a new technique for spatial profiling of DNA methylome and transcriptome in tissues [2]. - This technology allows for the generation of high-quality DNA-RNA dual-modal tissue maps, revealing how DNA methylation interacts with transcription to define cell identity and drive developmental programs [5][6]. Group 2: Biological Implications - DNA methylation is a key epigenetic mechanism that regulates gene expression and cell states, with abnormal patterns linked to various diseases, including cancer and autoimmune disorders [4]. - The study highlights the dynamic changes in DNA methylation across different cell types and developmental stages, providing insights into the molecular definitions of cell identity during mammalian development and brain function [5][6]. Group 3: Research Applications - The Spatial-DMT technology was applied to mouse embryos and postnatal mouse brains, allowing for the reconstruction of dynamic changes in the epigenome and transcriptome during embryonic development [6]. - The integration of spatial maps from different developmental stages reveals details of transcriptional regulation mediated by sequence, cell type, and region-specific methylation [6][7].