Table 1.
Overview of currently identified fibroblast subsets involved in wound healing and skin repair.
| Fibroblast subset | Location | Species | Characteristics | Reference |
|---|---|---|---|---|
| PDGFRA+, CD26+, SCA-, BLIMP1-, LRIG1+ | Papillary dermis | Mouse | Regenerative, contribution to hair follicle formation | (17) |
| PDGFRA+, DLK1+, SCA1- | Reticular dermis | Mouse | Profibrotic, wound-induced α-SMA expression | (17) |
| PDGFRA+, Dlk1+/-, Sca1+ | Hypodermal tissue | Mouse | Profibrotic | (17) |
| PDGFRA+, DLK1-, LRIG1+ | Dermis | Mouse | Fibroblast progenitor | (17) |
| PDGFRA+, BLIMP1+, DLK1-, LRIG1+ | Dermis | Mouse | Papillary fibroblast progenitor | (17) |
| PDGFRA+, BLIMP1-, DLK1+ | Dermis | Mouse | Reticular fibroblast progenitor | (17) |
| FAP+CD90- | Abdominal and breast, papillary dermis | Human | Regenerative, highly proliferative, PDPN, NTN1 expression | (65) |
| FAP-CD90+ | Abdominal and breast, reticular dermis | Human | Profibrotic, adipogenic, ACTA2, MGP, PPARg, CD36 expression | (65) |
| CD90+CD39+CD26- | Papillary dermis | Human | Regenerative, anti-inflammatory, support epidermis, expression of papillary markers COL6A5, WNT5A, RSPO1, and LEF1 | (40) |
| CD90+CD36+ | Reticular dermis | Human | Profibrotic, ECM production, include pre-adipocytes | (40) |
| CD90+CD39+CD26+ | Reticular dermis | Human | (40) | |
| CD90+CD39-RGS5-/+ | Reticular dermis | Human | (40) | |
| SFRP2+CD26+ | Arm | Human | Profibrotic, matrix production and deposition, major subpopulation | (75) |
| FMO1+ LSP1+ | Arm | Human | Regenerative, inflammatory cell retention, major subpopulation | (75) |
| COL11A1+ | Arm | Human | Connective tissue cell differentiation | (75) |
| CRABP1+ | Arm, dermal papilla | Human | Regulation of stem cell differentiation in the hair follicle bulge | (75) |
| SFRP4+ | Arm | Human | Possible progenitors of PCOLCE2+ and/or SFRP2+ cells | (75) |
| PRG4+ | Arm | Human | (75) | |
| PCOLCE2+ | Arm | Human | (75) | |
| PDGFRA+, CRABP1+ | Dorsal, upper dermis | Mouse | Profibrotic, Tgfbr2, Tgfbr3 expression | (74) |
| PDGFRA+, CRABP1- | Dorsal, lower dermis | Mouse | Regenerative, Tgfbr2, Tgfbr3 expression | (74) |
| PDGFRA-, PDGFRB+ | Dorsal | Mouse | 24% of wound fibroblasts 12 dpw | (74) |
| EN1 LIN+ FIBROBLASTS (“EPFS”) | Dorsal | Mouse | Profibrotic, drivers of fascia matrix migration | (4, 14) |
| EN1 LIN- FIBROBLASTS (“ENFS”) | Dorsal | Mouse | Regenerative | (4, 14) |
| WNT1 lin+ FIBROBLASTS (“WPFS”) | Oral | Mouse | Regenerative | (4) |
| PRRX1+ | Ventral | Mouse | Profibrotic | (15, 85) |
| PRRX1- | Ventral | Mouse | Regenerative | (15, 85) |
| SCA1+, CD34+, CD29+, EN1 LIN+ | Dorsal | Mouse | Profibrotic, myofibroblasts and adipocyte precursor cells | (51) |
| PDGFRA+, ADAM12+ | Ear, perivascular | Mouse | Profibrotic progenitor cells | (86) |
| CHURC1 | Ventral wounds | Mouse | Site-specific expression of developmental genes | (87) |
| WNT5A | Dorsal wounds | Mouse | Site-specific expression of developmental genes | (87) |
| MSX1 | Cheek wounds | Mouse | Site-specific expression of developmental genes | (87) |
To date, a plethora of fibroblast populations in the skin have been isolated, each of which exhibits unique phenotypic and functional characteristics. Different gene expression patterns and cell surface markers allow conclusions to be drawn about their distinct roles in cutaneous wound healing and regeneration. However, high variance in sample origins and disparities in methodology still limit the (inter)comparability, reproducibility, and continuation of previous research findings. Standardized and transferable protocols are, therefore, needed to streamline fibroblast research in the future.