دورية أكاديمية
Integrated spatial multiomics reveals fibroblast fate during tissue repair.
| العنوان: | Integrated spatial multiomics reveals fibroblast fate during tissue repair. |
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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.; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305., Januszyk M; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305., Yost KE; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305., Chinta MS; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., Gulati GS; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Nguyen AT; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., Burcham AR; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., Salhotra A; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Ransom RC; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Henn D; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., Chen K; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., Mascharak S; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Tolentino K; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305., Titan AL; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305., Jones RE; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., da Silva O; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., Leavitt WT; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., Marshall CD; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305., des Jardins-Park HE; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Hu MS; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305., Wan DC; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305., Wernig G; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Wagh D; Stanford Functional Genomics Facility, Stanford University, Stanford, CA 94305., Coller J; Stanford Functional Genomics Facility, Stanford University, Stanford, CA 94305., Norton JA; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305., Gurtner GC; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305.; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305., Newman AM; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305., Chang HY; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305; howchang@stanford.edu longaker@stanford.edu.; HHMI, Stanford University, Stanford, CA 94305., Longaker MT; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305; howchang@stanford.edu longaker@stanford.edu.; Department of Surgery, Stanford University School of Medicine, Stanford CA 94305.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Oct 12; Vol. 118 (41). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Cicatrix/*pathology , Fibroblasts/*metabolism , Fibrosis/*pathology , Skin/*injuries , Wound Healing/*physiology, Animals ; Cell Differentiation ; Cell Movement ; Cell Proliferation ; Extracellular Matrix/metabolism ; Female ; Mechanotransduction, Cellular/physiology ; Mice ; Mice, Inbred C57BL ; Skin/metabolism |
| مستخلص: | In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to skin injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to reveal potential mechanisms controlling fibroblast fate during migration, proliferation, and differentiation following skin injury, and thereby reexamine the canonical phases of wound healing. These findings have broad implications for the study of tissue repair in complex organ systems. Competing Interests: Competing interest statement: H.Y.C. is a co-founder of Accent Therapeutics, Boundless Bio, and an advisor of 10× Genomics, Arsenal Biosciences, and Spring Discovery. The entities had no role in the design, execution, or interpretation of this research. They had no role in the funding of this research. The paper reports basic research and has no financial implications for the listed companies. Two authors have co-published perspective or review articles with one reviewer over the last 4 y. (Copyright © 2021 the Author(s). Published by PNAS.) |
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| معلومات مُعتمدة: | R00 CA187192 United States CA NCI NIH HHS; F32 CA239312 United States CA NCI NIH HHS; K08 HL143143 United States HL NHLBI NIH HHS; R01 GM136659 United States GM NIGMS NIH HHS; R35 CA209919 United States CA NCI NIH HHS; S10 OD018220 United States OD NIH HHS; U01 DK119094 United States DK NIDDK NIH HHS; RM1 HG007735 United States HG NHGRI NIH HHS; R01 DE027346 United States DE NIDCR NIH HHS; P50 HG007735 United States HG NHGRI NIH HHS; K99 CA187192 United States CA NCI NIH HHS; R01 GM116892 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: chromatin accessibility; fibrosis; multiomics; spatial epigenomics; spatial transcriptomics |
| تواريخ الأحداث: | Date Created: 20211008 Date Completed: 20211214 Latest Revision: 20240405 |
| رمز التحديث: | 20240405 |
| مُعرف محوري في PubMed: | PMC8521719 |
| DOI: | 10.1073/pnas.2110025118 |
| PMID: | 34620713 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.2110025118 |