Genetic, epigenetic, and post‐transcriptional basis of divergent tissue regenerative capacities among vertebrates

Khyeam, Sheamin; Lee, Sukjun; Huang, Guo N.

doi:10.1002/ggn2.10042

Cited by 16 publications

(12 citation statements)

References 180 publications

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“…Instead, appendage amputation of adult mammals often heals the wounding by the formation of a fibrotic scar [ 1 , 2 , 3 , 4 , 5 ]. The observation of the appendage regenerating process in vertebrates reveals that epimorphic regeneration shares conserved histological events, including re-epithelization of the wound, formation of the blastema and growth of the different tissues [ 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…After 7–10 DPA, the blastema derived from dedifferentiated tissue or existing progenitor cells emerges near the distal end of the rupture site and gradually differentiates to form a replacement appendage after 30 DPA [ 10 , 11 , 12 ]. Accordingly, the underlying cellular and molecular mechanisms that govern the reconstruction of multi-tissue structures are highly overlapped [ 8 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Self-Control of Inflammation during Tail Regeneration of Lizards

Song

Wang

2021

JDB

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Lizards can spontaneously regenerate their lost tail without evoking excessive inflammation at the damaged site. In contrast, tissue/organ injury of its mammalian counterparts results in wound healing with a formation of a fibrotic scar due to uncontrolled activation of inflammatory responses. Unveiling the mechanism of self-limited inflammation occurring in the regeneration of a lizard tail will provide clues for a therapeutic alternative to tissue injury. The present review provides an overview of aspects of rapid wound healing and roles of antibacterial peptides, effects of leukocytes on the tail regeneration, self-blocking of the inflammatory activation in leukocytes, as well as inflammatory resistance of blastemal cells or immature somatic cells during lizard tail regeneration. These mechanistic insights of self-control of inflammation during lizard tail regeneration may lead in the future to the development of therapeutic strategies to fight injury-induced inflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Self-Control of Inflammation during Tail Regeneration of Lizards

Song

Wang

2021

JDB

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“…Despite the role of agr2 in newt limb regeneration being established ( Kumar et al, 2007 ; Grassme et al, 2016 ) and elevated expression of ag1 and agr2 being shown during the regeneration of the frog ( Xenopus laevis) tadpoles limbs and tails ( Ivanova et al, 2013 ), it is still unknown whether these two genes also play critical roles in frogs’ regeneration abilities. Additionally, answering this question would contribute to a better understanding of whether the disappearance of ag1 in the evolutionary younger vertebrate species, in particular in mammals, could be one of the critical reasons for the sharp decline in their ability to regenerate body appendages ( Khyeam et al, 2021 ). Previously, we hypothesized and presented evidence that such a decline, as observed in groups of animals that appeared later in the evolution than amphibians, could be the result of the loss of some genes in their ancestors, which still regulate regeneration in the extant fishes and amphibians ( Ivanova et al, 2013 , 2015 , 2018 ; Korotkova et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The Secreted Protein Disulfide Isomerase Ag1 Lost by Ancestors of Poorly Regenerating Vertebrates Is Required for Xenopus laevis Tail Regeneration

Ivanova

Tereshina

Araslanova

et al. 2021

Front. Cell Dev. Biol.

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Warm-blooded vertebrates regenerate lost limbs and their parts in general much worse than fishes and amphibians. We previously hypothesized that this reduction in regenerative capability could be explained in part by the loss of some genes important for the regeneration in ancestors of warm-blooded vertebrates. One of such genes could be ag1, which encodes secreted protein disulfide isomerase of the Agr family. Ag1 is activated during limb and tail regeneration in the frog Xenopus laevis tadpoles and is absent in warm-blooded animals. The essential role of another agr family gene, agr2, in limb regeneration was demonstrated previously in newts. However, agr2, as well as the third member of agr family, agr3, are present in all vertebrates. Therefore, it is important to verify if the activity of ag1 lost by warm-blooded vertebrates is also essential for regeneration in amphibians, which could be a further argument in favor of our hypothesis. Here, we show that in the Xenopus laevis tadpoles in which the expression of ag1 or agr2 was artificially suppressed, regeneration of amputated tail tips was also significantly reduced. Importantly, overexpression of any of these agrs or treatment of tadpoles with any of their recombinant proteins resulted in the restoration of tail regeneration in the refractory period when these processes are severely inhibited in normal development. These findings demonstrate the critical roles of ag1 and agr2 in regeneration in frogs and present indirect evidence that the loss of ag1 in evolution could be one of the prerequisites for the reduction of regenerative ability in warm-blooded vertebrates.

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“…This approach can also be important for regenerative medicine. The regenerative capacity is higher in simpler organisms [ 31 , 32 ]. Therefore, the controlled activation of earlier metazoan programs may facilitate injury healing and rejuvenation.…”

Section: Introductionmentioning

confidence: 99%

Growth of Biological Complexity from Prokaryotes to Hominids Reflected in the Human Genome

Vinogradov

Anatskaya

2021

IJMS

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The growth of complexity in evolution is a most intriguing phenomenon. Using gene phylostratigraphy, we showed this growth (as reflected in regulatory mechanisms) in the human genome, tracing the path from prokaryotes to hominids. Generally, the different regulatory gene families expanded at different times, yet only up to the Euteleostomi (bony vertebrates). The only exception was the expansion of transcription factors (TF) in placentals; however, we argue that this was not related to increase in general complexity. Surprisingly, although TF originated in the Prokaryota while chromatin appeared only in the Eukaryota, the expansion of epigenetic factors predated the expansion of TF. Signaling receptors, tumor suppressors, oncogenes, and aging- and disease-associated genes (indicating vulnerabilities in terms of complex organization and strongly enrichment in regulatory genes) also expanded only up to the Euteleostomi. The complexity-related gene properties (protein size, number of alternative splicing mRNA, length of untranslated mRNA, number of biological processes per gene, number of disordered regions in a protein, and density of TF–TF interactions) rose in multicellular organisms and declined after the Euteleostomi, and possibly earlier. At the same time, the speed of protein sequence evolution sharply increased in the genes that originated after the Euteleostomi. Thus, several lines of evidence indicate that molecular mechanisms of complexity growth were changing with time, and in the phyletic lineage leading to humans, the most salient shift occurred after the basic vertebrate body plan was fixed with bony skeleton. The obtained results can be useful for evolutionary medicine.

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Genetic, epigenetic, and post‐transcriptional basis of divergent tissue regenerative capacities among vertebrates

Cited by 16 publications

References 180 publications

Self-Control of Inflammation during Tail Regeneration of Lizards

Self-Control of Inflammation during Tail Regeneration of Lizards

The Secreted Protein Disulfide Isomerase Ag1 Lost by Ancestors of Poorly Regenerating Vertebrates Is Required for Xenopus laevis Tail Regeneration

Growth of Biological Complexity from Prokaryotes to Hominids Reflected in the Human Genome

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