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Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin.
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.
Affiliation
  • Foster DS; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
  • Januszyk M; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Delitto D; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
  • Yost KE; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Griffin M; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Guo J; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Guardino N; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Delitto AE; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
  • Chinta M; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Burcham AR; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Nguyen AT; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Bauer-Rowe KE; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Titan AL; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
  • Salhotra A; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Jones RE; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • da Silva O; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Lindsay HG; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Berry CE; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Chen K; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Henn D; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Mascharak S; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Talbott HE; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Kim A; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Nosrati F; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Sivaraj D; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Ransom RC; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Matthews M; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Khan A; Cell Sciences Imaging Facility, Stanford University, Stanford, CA 94305, USA.
  • Wagh D; Stanford Genomics Facility, Stanford University, Stanford, CA 94305, USA.
  • Coller J; Stanford Genomics Facility, Stanford University, Stanford, CA 94305, USA.
  • Gurtner GC; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
  • Wan DC; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
  • Wapnir IL; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA.
  • Chang HY; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. Electronic address: howchang@stanford.edu.
  • Norton JA; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA. Electronic address: janorton@stanford.edu.
  • Longaker MT; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305, USA; Institute for Stem Cell Biology and Regenerati
Cancer Cell ; 40(11): 1392-1406.e7, 2022 11 14.
Article in En | MEDLINE | ID: mdl-36270275
ABSTRACT
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.
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Full text: 1 Database: MEDLINE Main subject: Cancer-Associated Fibroblasts / Neoplasms Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2022 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Cancer-Associated Fibroblasts / Neoplasms Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2022 Type: Article Affiliation country: United States