Human fetal dermal fibroblast-myeloid cell diversity is characterized by dominance of pro-healing Annexin1-FPR1 signaling
Rajneesh Srivastava,
Kanhaiya Singh,
Ahmed S. Abouhashem,
Manishekhar Kumar,
Sedat Kacar,
Sumit S. Verma,
Sujit K. Mohanty,
Mithun Sinha,
Subhadip Ghatak,
Yi Xuan,
Chandan K. Sen
Affiliations
Rajneesh Srivastava
McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA
Kanhaiya Singh
McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA; Corresponding author
Ahmed S. Abouhashem
Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA; Sharkia Clinical Research Department, Ministry of Health, Zagazig, Egypt
Manishekhar Kumar
McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA
Sedat Kacar
Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA
Sumit S. Verma
McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA
Sujit K. Mohanty
McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA
Mithun Sinha
Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA
Subhadip Ghatak
McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA
Yi Xuan
McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA
Chandan K. Sen
McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Indiana University School of Medicine, Indianapolis, IN, USA; Corresponding author
Summary: Fetal skin achieves scarless wound repair. Dermal fibroblasts play a central role in extracellular matrix deposition and scarring outcomes. Both fetal and gingival wound repair share minimal scarring outcomes. We tested the hypothesis that compared to adult skin fibroblasts, human fetal skin fibroblast diversity is unique and partly overlaps with gingival skin fibroblasts. Human fetal skin (FS, n = 3), gingiva (HGG, n = 13), and mature skin (MS, n = 13) were compared at single-cell resolution. Dermal fibroblasts, the most abundant cluster, were examined to establish a connectome with other skin cells. Annexin1-FPR1 signaling pathway was dominant in both FS as well as HGG fibroblasts and related myeloid cells while scanty in MS fibroblasts. Myeloid-specific FPR1-ORF delivered in murine wound edge using tissue nanotransfection (TNT) technology significantly enhanced the quality of healing. Pseudotime analyses identified the co-existence of an HGG fibroblast subset with FPR1high myeloid cells of fetal origin indicating common underlying biological processes.
