| Data source |
SRA: PRJNA559885
|
| Description |
The ability to regenerate body parts lost to amputation is widely but non-uniformly distributed in animals. Species such as bony fishes display extensive regenerative capacities, while others such as mammals regenerate poorly. Even though regeneration has been the subject of extensive phylogenetic, developmental, cellular and molecular studies, the mechanisms underlying the broad disparity of regenerative capacities in animals remain elusive. Here we report on a comparative epigenomic and transcriptomic approach which identified an evolutionarily conserved regeneration response program in vertebrates. By defining the cis-regulomes and single-cell transcriptomes of early stages of regeneration in the distantly related African killifish Nothobranchius furzeri and the zebrafish Danio rerio, we uncovered species-specific and evolutionarily conserved genomic responses to amputation. |
| Key word |
transcription factors; tissue regeneration; zebrafish; genome; activin; evolution; insights; injury; transgenesis; methylations |
| Publication |
Wang, Wei, et al. "Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates." Science 369.6508 (2020): eaaz3090. |
| Abstract |
Vertebrates vary in their ability to regenerate, and the genetic mechanisms underlying such disparity remain elusive. Comparative epigenomic profiling and single-cell sequencing of two related teleost fish uncovered species-specific and evolutionarily conserved genomic responses to regeneration. The conserved response revealed several regeneration-responsive enhancers (RREs), including an element upstream to inhibin beta A (inhba), a known effector of vertebrate regeneration. This element activated expression in regenerating transgenic fish, and its genomic deletion perturbed caudal fin regeneration and abrogated cardiac regeneration altogether. The enhancer is present in mammals, shares functionally essential activator protein 1 (AP-1)-binding motifs, and responds to injury, but it cannot rescue regeneration in fish. This work suggests that changes in AP-1-enriched RREs are likely a crucial source of loss of regenerative capacities in vertebrates. |
