Fibroblast dedifferentiation as a determinant of successful regeneration

Abstract

Highlights d Fibroblast-derived Prrx1 + cells are the main constituent of a frog limb blastema d Frog fibroblasts only undergo partial dedifferentiation due to intrinsic limitations d Adult chondrogenesis is distinct from the embryonic program

Appendage regeneration is context dependent at the cellular level

“…Meanwhile, the second possibility would indicate establishing new gene regulatory networks that are not observed during development and potentially exhibit new functions. Based on the latest single-cell transcriptomics results from different species ( Xenopus [ 45 , 88 ], mouse [ 21 ] and the axolotl [ 80 ]), specific fibroblast cells express genes associated with blastema and show transcriptional programmes that are not seen during limb development. More specifically, in froglets, amputation was shown to induce a subset of fibroblasts to initiate a chondrogenic transcriptional programme that is different than the chondrogenic programme during limb development [ 88 ].…”

“…Based on the latest single-cell transcriptomics results from different species ( Xenopus [ 45 , 88 ], mouse [ 21 ] and the axolotl [ 80 ]), specific fibroblast cells express genes associated with blastema and show transcriptional programmes that are not seen during limb development. More specifically, in froglets, amputation was shown to induce a subset of fibroblasts to initiate a chondrogenic transcriptional programme that is different than the chondrogenic programme during limb development [ 88 ]. Hence, the previous terminology labelling so-called dedifferentiated cells could be indicating an injury-induced cell state for some fibroblast cell types rather than resetting to a developmental cell state.…”

Furnishing Wound Repair by the Subcutaneous Fascia

“…By performing transplantation and cell-fate tracing using chimeric froglets that have GFP-negative skin and GFP-labeled subcutaneous fascial tissues, Otsuka-Yamaguchi and colleagues found that subcutaneous fascial cells became blastema-like cells with activated Prrx1 limb enhancer, and contributed to regenerating the skin, especially the dermis, after an excision injury [84]. Recently, Prrx1 + fibroblasts have been shown to be responsible for scar formation of the ventral skin in mice [85], but a determinant of a successful limb regeneration in Xenopus laevis [86]. Therefore, understanding the key similarities and differences in fascial fibroblasts between mammals and lower vertebrates may provide molecular and cellular insights into scarless wound healing.…”

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

“…In addition to the cells’ differentiation, de-differentiation has also been involved in repairing cell stress, and is mediated by the EMT or MET [ 3 , 73 ]. Such processes can be easily found in the transition of myofibroblasts and fibroblasts [ 25 ]. Multiple cell resources have been identified to be able to transform into myofibroblasts under cell stress or injury.…”

“…Additionally, a similar processes of EMT can be observed when internal organ damage occurs [ 23 ], and some epithelium undergoes trans-differentiation to repair the damaged part [ 24 ]. When tissues are wounded, these phenomena can easily be observed in the whole body or on the skin or body surface, where epithelial trans-differentiation into mesenchymal cells with cell mobility occurs [ 25 ]. Mesenchymal cells come to the wound region to form an intact barrier and transform into epithelial cells during the “wound healing process” [ 26 ].…”