Poised Regeneration of Zebrafish Melanocytes Involves Direct Differentiation and Concurrent Replenishment of Tissue-Resident Progenitor Cells

Abstract

SUMMARY Efficient regeneration following injury is critical for maintaining tissue function and enabling organismal survival. Cells reconstituting damaged tissue are often generated from resident stem or progenitor cells or from cells that have dedifferentiated and become proliferative. While lineage-tracing studies have defined cellular sources of regeneration in many tissues, the process by which these cells execute the regenerative process is largely obscure. Here, we have identified tissue-resident progenitor cells that mediate regeneration of zebrafish stripe melanocytes and defined how these cells reconstitute pigmentation. Nearly all regeneration melanocytes arise through direct differentiation of progenitor cells. Wnt signaling is activated prior to differentiation, and inhibition of Wnt signaling impairs regeneration. Additional progenitors divide symmetrically to sustain the pool of progenitor cells. Combining direct differentiation with symmetric progenitor divisions may serve as a means to rapidly repair injured tissue while preserving the capacity to regenerate.

Regeneration of the zebrafish retinal pigment epithelium after widespread genetic ablation

“…The rate and peripheral-to-central pattern of RPE regeneration suggest that regeneration is driven by cell proliferation, and not simply an expansion of RPE, a response noted in several systems after small injuries (19,26,41). Proliferative cells are a major component of regeneration in diverse tissues, and they often derive from a resident pool of progenitor cells (42,43), or from differentiated cells that are stimulated to respond to injury (33,44). Moreover, RPE proliferation results from loss of BM contact in several injury contexts, and pathologically, during PVR (19,25,45).…”

Pre-existent adult sox10+cardiomyocytes contribute to myocardial regeneration in the zebrafish

“…Adult neural crest stem cells have been recently proposed as the source of progenitor cells during adult pigment cell regeneration in the zebrafish (Iyengar, et al, 2015).…”

Spatiotemporal Labeling of Melanocytes in Mice

“…Glover et al further went on to develop another transgenic mouse model ( Rosa26::mT/mG ) in which the Rosa26 promoter ubiquitously drives the membrane expression of tdTomato (red) in all cells, but switches to green membrane fluorescence (EGFP) upon Cre- mediated recombination and the excision of tdTomato [ 47 ]. In another model of zebrafish, Iyengar et al utilized FUCCI reporter system to demonstrate that unpigmented mitfa -expressing cells directly differentiate into melanocytes during regeneration upon the activation of Wnt signaling [ 71 ]. Thus, these newer transgenic mouse models that incorporate FUCCI based reporter system are a valuable tool and make fluorescent imaging as well as isolation very convenient in tiny cell populations, such as melanocytes.…”