학술논문
Single-cell mapping of regenerative and fibrotic healing responses after musculoskeletal injury.
Document Type
Academic Journal
Author
Tower RJ; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: robert.tower@utsouthwestern.edu.; Bancroft AC; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Chowdary AR; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Barnes S; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Bioinformatics Core, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Edwards NJ; Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.; Pagani CA; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Dawson LA; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.; Levi B; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: benjamin.levi@utsouthwestern.edu.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101611300 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-6711 (Electronic) Linking ISSN: 22136711 NLM ISO Abbreviation: Stem Cell Reports Subsets: MEDLINE
Subject
Language
English
Abstract
After injury, a cascade of events repairs the damaged tissue, including expansion and differentiation of the progenitor pool and redeposition of matrix. To guide future wound regeneration strategies, we compared single-cell sequencing of regenerative (third phalangeal element [P3]) and fibrotic (second phalangeal element [P2]) digit tip amputation (DTA) models as well as traumatic heterotopic ossification (HO; aberrant). Analyses point to a common initial response to injury, including expansion of progenitors, redeposition of matrix, and activation of transforming growth factor β (TGF-β) and WNT pathways. Surprisingly, fibrotic P2 DTA showed greater transcriptional similarity to HO than to regenerative P3 DTA, suggesting that gene expression more strongly correlates with healing outcome than with injury type or cell origin. Differential analysis and immunostaining revealed altered activation of inflammatory pathways, such as the complement pathway, in the progenitor cells. These data suggests that common pathways are activated in response to damage but are fine tuned within each injury. Modulating these pathways may shift the balance toward regenerative outcomes.
Competing Interests: Conflict of interests The authors declare no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Competing Interests: Conflict of interests The authors declare no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)