دورية أكاديمية
Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin.
| العنوان: | Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin. |
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| المؤلفون: | 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 Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: longaker@stanford.edu. |
| المصدر: | Cancer cell [Cancer Cell] 2022 Nov 14; Vol. 40 (11), pp. 1392-1406.e7. Date of Electronic Publication: 2022 Oct 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | Cancer-Associated Fibroblasts*/pathology , Neoplasms*/genetics , Neoplasms*/pathology, Humans ; Proteomics ; Tumor Microenvironment/genetics ; Phenotype |
| مستخلص: | 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. Competing Interests: Declaration of interests D.S.F., M.J., D.D., H.Y.C., J.A.N., and M.T.L. have applied for a provisional patent through Stanford University related to the research presented in this manuscript. H.Y.C. is a co-founder of Accent Therapeutics, Boundless Bio, and Cartography Biosciences, and an advisor of 10X Genomics, Arsenal Biosciences, and Spring Discovery. K.E.Y. is a consultant for Cartography Biosciences. (Copyright © 2022 Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Cancer Cell. 2022 Nov 14;40(11):1273-1275. (PMID: 36379205) |
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| معلومات مُعتمدة: | S10 OD025212 United States OD NIH HHS; F32 CA239312 United States CA NCI NIH HHS; R01 DE027346 United States DE NIDCR NIH HHS; S10 OD010580 United States OD NIH HHS; R01 GM136659 United States GM NIGMS NIH HHS; R35 CA209919 United States CA NCI NIH HHS; R01 GM116892 United States GM NIGMS NIH HHS; U01 DK119094 United States DK NIDDK NIH HHS; RM1 HG007735 United States HG NHGRI NIH HHS; S10 OD018220 United States OD NIH HHS; P30 CA124435 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: ATAC-seq; CODEX; RNA-seq; cancer; fibroblasts; mechanotransduction; multi-omics; single cell; spatial transcriptomics |
| تواريخ الأحداث: | Date Created: 20221021 Date Completed: 20221118 Latest Revision: 20231116 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9669239 |
| DOI: | 10.1016/j.ccell.2022.09.015 |
| PMID: | 36270275 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-3686 |
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| DOI: | 10.1016/j.ccell.2022.09.015 |