Project description:Pancreatic ductal adenocarcinoma (PDAC) remains resistant to most treatments and demonstrates a complex pathobiology. Here, we deconvolute regional heterogeneity in the human PDAC tumor microenvironment (TME), a long-standing obstacle, to define precise stromal contributions to PDAC progression. Large scale integration of histology-guided multiOMICs profiling with clinical data sets and functional in vitro models uncovered two microenvironmental programs in PDAC that were anchored in fibroblast differentiation states. These sub-tumor microenvironments (subTMEs) co-occurred intratumorally and were spatially confined, producing patient-specific cellular and molecular heterogeneity associated with shortened patient survival. Each subTME was uniquely structured to support discrete aspects of tumor biology: reactive regions rich in activated fibroblast communities were immune-hot and promoted aggressive tumor progression while deserted regions enriched in extracellular matrix supported tumor differentiation yet were markedly chemoprotective. In conclusion, PDAC regional heterogeneity derives from biologically distinct reactive and protective TME elements with a defined, active role in PDAC progression.

2021-08-23 | GSE166571 | GEO

Spatially confined folding of chromatin in the interphase nucleus.

Project description: Not available

| S-EPMC2656162 | biostudies-literature

Neutral glycans from sandfish skin can reduce friction of polymers.

Project description: Not available

| S-EPMC4843684 | biostudies-literature

Selective C-C Coupling by Spatially Confined Dimeric Metal Centers.

Project description: Not available

| S-EPMC7183208 | biostudies-literature

Stress generation, relaxation and size control in confined tumor growth.

Project description: Not available