biostudies-literatureHandler KLeona M. and Harry B. Helmsley Charitable Trust (Helmsley Charitable Trust)Leona M. and Harry B. Helmsley Charitable TrustSwiss National Science Foundation7775https://www.ebi.ac.uk/biostudies/studies/S-EPMC10681997biostudies-literatureUnknown14(1)Cells collectively determine biological functions by communicating with each other-both through direct physical contact and secreted factors. Consequently, the local microenvironment of a cell influences its behavior, gene expression, and cellular crosstalk. Disruption of this microenvironment causes reciprocal changes in those features, which can lead to the development and progression of diseases. Hence, assessing the cellular transcriptome while simultaneously capturing the spatial relationships of cells within a tissue provides highly valuable insights into how cells communicate in health and disease. Yet, methods to probe the transcriptome often fail to preserve native spatial relationships, lack single-cell resolution, or are highly limited in throughput, i.e. lack the capacity to asNature communicationsFragment-sequencing unveils local tissue microenvironments at single-cell resolution.PMC10681997Gut Cell Atlas181249Handler KBorrelli CFicht XMoor AEPiscuoglio SAcar IEBach KfalseFragment-sequencing unveils local tissue microenvironments at single-cell resolution.Cells collectively determine biological functions by communicating with each other-both through direct physical contact and secreted factors. Consequently, the local microenvironment of a cell influences its behavior, gene expression, and cellular crosstalk. Disruption of this microenvironment causes reciprocal changes in those features, which can lead to the development and progression of diseases. Hence, assessing the cellular transcriptome while simultaneously capturing the spatial relationships of cells within a tissue provides highly valuable insights into how cells communicate in health and disease. Yet, methods to probe the transcriptome often fail to preserve native spatial relationships, lack single-cell resolution, or are highly limited in throughput, i.e. lack the capacity to as2023-01-01T00:00:00Z2023 Nov2025-04-05T10:24:01.608Z2025-02-19T04:44:07.077ZS-EPMC106819973801214910.1038/s41467-023-43005-8