Integrated spatial multiomics reveals fibroblast fate during tissue repair.
IF: 12.779
Cited by: 53


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.


Spatial Genomics
Spatial Epigenomics
Spatial Transcriptomics
chromatin accessibility
spatial epigenomics
spatial transcriptomics

MeSH terms

Cell Differentiation
Cell Movement
Cell Proliferation
Extracellular Matrix
Mechanotransduction, Cellular
Mice, Inbred C57BL
Wound Healing


Foster, Deshka S
Januszyk, Michael
Yost, Kathryn E
Chinta, Malini S
Gulati, Gunsagar S
Nguyen, Alan T
Burcham, Austin R
Salhotra, Ankit
Ransom, R Chase
Henn, Dominic
Chen, Kellen
Mascharak, Shamik
Tolentino, Karen
Titan, Ashley L
Jones, R Ellen
da Silva, Oscar
Leavitt, W Tripp
Marshall, Clement D
des Jardins-Park, Heather E
Hu, Michael S
Wan, Derrick C
Wernig, Gerlinde
Wagh, Dhananjay
Coller, John
Norton, Jeffrey A
Gurtner, Geoffrey C
Newman, Aaron M
Chang, Howard Y
Longaker, Michael T

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