
Integrated spatial multiomics reveals fibroblast fate during tissue repair
Author(s) -
Deshka S. Foster,
Michael Januszyk,
Kathryn E. Yost,
Malini Chinta,
Gunsagar S. Gulati,
Alan Nguyen,
Austin Burcham,
Ankit Salhotra,
Ryan C. Ransom,
Dominic Henn,
Kellen Chen,
Shamik Mascharak,
Karen Tolentino,
Ashley L. Titan,
Ruth Ellen Jones,
Oscar da Silva,
Tripp Leavitt,
Clement D. Marshall,
Heather E. Des Jardins-Park,
Michael S. Hu,
Derrick C. Wan,
Gerlinde Wernig,
Dhananjay Wagh,
John A. Coller,
Jeffrey A. Norton,
Geoffrey C. Gurtner,
Aaron M. Newman,
Howard Y. Chang,
Michael T. Longaker
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2110025118
Subject(s) - fibroblast , extracellular matrix , fibrosis , wound healing , regeneration (biology) , microbiology and biotechnology , biology , cell , tissue repair , cell migration , pathology , immunology , medicine , cell culture , genetics
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.