Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin.
IF: 38.585
Cited by: 28


Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach. Using paired, same-cell chromatin accessibility and transcriptome analysis, we provided an integrated analysis of CAF subpopulations over a complex spatial transcriptomic and proteomic landscape to identify three superclusters: steady state-like (SSL), mechanoresponsive (MR), and immunomodulatory (IM) CAFs. These superclusters are recapitulated across multiple tissue types and species. Selective disruption of underlying mechanical force or immune checkpoint inhibition therapy results in shifts in CAF subpopulation distributions and affected tumor growth. As such, the balance among CAF superclusters may have considerable translational implications. Collectively, this research expands our understanding of CAF biology, identifying regulatory pathways in CAF differentiation and elucidating therapeutic targets in a species- and tumor-agnostic manner.


Spatial Transcriptomics
single cell
spatial transcriptomics

MeSH terms

Cancer-Associated Fibroblasts
Tumor Microenvironment


Foster, Deshka S
Januszyk, Michael
Delitto, Daniel
Yost, Kathryn E
Griffin, Michelle
Guo, Jason
Guardino, Nicholas
Delitto, Andrea E
Chinta, Malini
Burcham, Austin R
Nguyen, Alan T
Bauer-Rowe, Khristian E
Titan, Ashley L
Salhotra, Ankit
Jones, R Ellen
da Silva, Oscar
Lindsay, Hunter G
Berry, Charlotte E
Chen, Kellen
Henn, Dominic
Mascharak, Shamik
Talbott, Heather E
Kim, Alexia
Nosrati, Fatemeh
Sivaraj, Dharshan
Ransom, R Chase
Matthews, Michael
Khan, Anum
Wagh, Dhananjay
Coller, John
Gurtner, Geoffrey C
Wan, Derrick C
Wapnir, Irene L
Chang, Howard Y
Norton, Jeffrey A
Longaker, Michael T