Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of a regeneration-organizing cell in the Xenopus tail.

ABSTRACT: Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential. To characterize this regenerative response, we performed single-cell RNA sequencing after tail amputation. By comparing naturally occurring regeneration-competent and -incompetent tadpoles, we identified a previously unrecognized cell type, which we term the regeneration-organizing cell (ROC). ROCs are present in the epidermis during normal tail development and specifically relocalize to the amputation plane of regeneration-competent tadpoles, forming the wound epidermis. Genetic ablation or manual removal of ROCs blocks regeneration, whereas transplantation of ROC-containing grafts induces ectopic outgrowths in early embryos. Transcriptional profiling revealed that ROCs secrete ligands associated with key regenerative pathways, signaling to progenitors to reconstitute lost tissue. These findings reveal the cellular mechanism through which ROCs form the wound epidermis and ensure successful regeneration.

SUBMITTER: Aztekin C

PROVIDER: S-EPMC6986927 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Identification of a regeneration-organizing cell in the Xenopus tail.

Aztekin C C Hiscock T W TW Marioni J C JC Gurdon J B JB Simons B D BD Jullien J J

Science (New York, N.Y.) 20190501 6441

Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential. To characterize this regenerative response, we performed single-cell RNA sequencing after tail amputation. By comparing naturally occurring regeneration-competent and -incompetent tadpoles, we identified a previously unrecognized cell type, which we term the regeneration-organizing cell (ROC). ROCs are present in the epidermis during normal tail development and specifically relocalize to the amputation plane of re ...[more]

PMID: 31097661

Similar Datasets

Early redox activities modulate Xenopus tail regeneration.

Project description:Redox state sustained by reactive oxygen species (ROS) is crucial for regeneration; however, the interplay between oxygen (O2), ROS and hypoxia-inducible factors (HIF) remains elusive. Here we observe, using an optic-based probe (optrode), an elevated and steady O2 influx immediately upon amputation. The spatiotemporal O2 influx profile correlates with the regeneration of Xenopus laevis tadpole tails. Inhibition of ROS production but not ROS scavenging decreases O2 influx. Inhibition of HIF-1α impairs regeneration and stabilization of HIF-1α induces regeneration in the refractory period. In the regeneration bud, hypoxia correlates with O2 influx, ROS production, and HIF-1α stabilization that modulate regeneration. Further analyses reveal that heat shock protein 90 is a putative downstream target of HIF-1α while electric current reversal is a de facto downstream target of HIF-1α. Collectively, the results show a mechanism for regeneration via the orchestration of O2 influx, ROS production, and HIF-1α stabilization.

| S-EPMC6191437 | biostudies-literature

Evolutionary divergence in tail regeneration between Xenopus laevis and Xenopus tropicalis.

Project description:Tissue regeneration is of fast growing importance in the development of biomedicine, particularly organ replacement therapies. Unfortunately, many human organs cannot regenerate. Anuran Xenopus laevis has been used as a model to study regeneration as many tadpole organs can regenerate. In particular, the tail, which consists of many axial and paraxial tissues, such as spinal cord, dorsal aorta and muscle, commonly present in vertebrates, can fully regenerate when amputated at late embryonic stages and most of the tadpole stages. Interestingly, between stage 45 when feeding begins to stage 47, the Xenopus laevis tail cannot regenerate after amputation. This period, termed "refractory period", has been known for about 20 years. The underlying molecular and genetic basis is unclear in part due to the difficult to carry out genetic studies in this pseudo-tetraploid species. Here we compared tail regeneration between Xenopus laevis and the highly related diploid anuran Xenopus tropicalis and found surprisingly that Xenopus tropicalis lacks the refractory period. Further molecular and genetic studies, more feasible in this diploid species, should reveal the basis for this evolutionary divergence in tail regeneration between two related species and facilitate the understanding how tissue regenerative capacity is controlled, thus with important implications for human regenerative medicine.

| S-EPMC8028753 | biostudies-literature

HDAC activity is required during Xenopus tail regeneration.

Project description:The ability to fully restore damaged or lost organs is present in only a subset of animals. The Xenopus tadpole tail is a complex appendage, containing epidermis, muscle, nerves, spinal cord, and vasculature, which regenerates after amputation. Understanding the mechanisms of tail regeneration may lead to new insights to promote biomedical regeneration in non-regenerative tissues. Although chromatin remodeling is known to be critical for stem cell pluripotency, its role in complex organ regeneration in vivo remains largely uncharacterized. Here we show that histone deacetylase (HDAC) activity is required for the early stages of tail regeneration. HDAC1 is expressed during the 1(st) two days of regeneration. Pharmacological blockade of HDACs using Trichostatin A (TSA) increased histone acetylation levels in the amputated tail. Furthermore, treatment with TSA or another HDAC inhibitor, valproic acid, specifically inhibited regeneration. Over-expression of wild-type Mad3, a transcriptional repressor known to associate in a complex with HDACs via Sin3, inhibited regeneration. Similarly, expression of a Mad3 mutant lacking the Sin3-interacting domain that is required for HDAC binding also blocks regeneration, suggesting that HDAC and Mad3 may act together to regulate regeneration. Inhibition of HDAC function resulted in aberrant expression of Notch1 and BMP2, two genes known to be required for tail regeneration. Our results identify a novel early role for HDAC in appendage regeneration and suggest that modulation of histone acetylation is important in regenerative repair of complex appendages.

| S-EPMC3194833 | biostudies-literature

Correction to: Evolutionary divergence in tail regeneration between Xenopus laevis and Xenopus tropicalis.

Project description: Not available

| S-EPMC8178875 | biostudies-literature

RNA-Seq of Xenopus tail regeneration

Project description:In contrast to humans, many amphibians are able to rapidly and completely regenerate complex tissues, including complete appendages. Following tail amputation, Xenopus tropicalis tadpoles quickly regenerate muscle, spinal cord, cartilage, vasculature and skin, all properly patterned in three dimensions. To better understand the molecular basis of this regenerative competence, we performed a transcriptional analysis of regeneration using RNA-Seq. We profiled the transcriptome at 6 timepoints during tail regeneration, and used clustering analysis to identify biological processes that are prioritized during different transitions in the regeneration process. Our work expands significantly on previous expression analyses of tail regeneration. We are able to refine the windows during which many key biological signaling processes act, including embryonic patterning signals, immune responses, bioelectrical signaling and apoptosis. By including multiple timepoints within the first 24 hours post-amputation, we have also identified new processes that are highly prioritized early in regeneration, including axonogenesis, chemotaxis, and RNA metabolism. Our work provides a deep database for researchers interested in appendage regeneration, and highlights new avenues for further study.

2017-01-30 | GSE88975 | GEO

ATAC-Seq of Xenopus tail regeneration

Project description:Mammals possess limited regeneration capabilities, where the few examples of scarless healing tend to be restricted to early development. In light of this, it is of great interest to study animals that can faithfully regrow complete appendages, and uncover the biological properties that facilitate this process. Xenopus tropicalis tadpoles are excellent vertebrate models of regeneration, as they rapidly recover lost tails within just one week post amputation. Though we have some understanding of what pathways are required for tail regeneration, we have yet to systematically chronicle the regulatory events that coordinate this specialized response to injury. Here, we highlight a striking phenomenon in Xenopus regeneration, whereby nuclei within the fin epithelium of an amputated tail change shape in a dramatic and stereotyped manner during regeneration. We assess chromatin accessibility dynamics through ATAC-Seq of nine time points of regeneration, and find that large scale changes in chromatin state are highly correlated to changes in nuclear shape. To identify critical regulators of these chromatin dynamics, we describe and apply a machine learning method, PFBoost, which integrates information from motifs underlying dynamically accessible ATAC-Seq peaks and differentially expressed transcription factors from time-matched RNA-Seq data to predict chromatin state. To functionally evaluate PFBoost-predicted regeneration regulators, we developed an inducible CRISPRi system utilizing the FKBP derived destabilizing domain, and knockdown expression of these regulators during the early hours of regeneration. With this methodology, we identified and describe two novel regulators of regeneration, spib and chd8. We provide not only an abundant resource for chromatin dynamics in tail regeneration, but also chronicle an intriguing mechanism of regeneration regulation in the form of nuclear shape change and coordinate changes in chromatin state.

2020-01-31 | GSE138303 | GEO

interleukin-11 induces and maintains progenitors of different cell lineages during Xenopus tadpole tail regeneration.

Project description:Unlike mammals, Xenopus laevis tadpoles possess high ability to regenerate their lost organs. In amphibians, the main source of regenerated tissues is lineage-restricted tissue stem cells, but the mechanisms underlying induction, maintenance and differentiation of these stem/progenitor cells in the regenerating organs are poorly understood. We previously reported that interleukin-11 (il-11) is highly expressed in the proliferating cells of regenerating Xenopus tadpole tails. Here, we show that il-11 knockdown (KD) shortens the regenerated tail length, and the phenotype is rescued by forced-il-11-expression in the KD tadpoles. Moreover, marker genes for undifferentiated notochord, muscle, and sensory neurons are downregulated in the KD tadpoles, and the forced-il-11-expression in intact tadpole tails induces expression of these marker genes. Our findings demonstrate that il-11 is necessary for organ regeneration, and suggest that IL-11 plays a key role in the induction and maintenance of undifferentiated progenitors across cell lineages during Xenopus tail regeneration. Xenopus laevis tadpoles have maintained their ability to regenerate various organs. Here, the authors show that interleukin-11 is necessary for organ regeneration, by inducing and maintaining undifferentiated progenitors across cell lineages during Xenopus tail regeneration.

| S-EPMC5591189 | biostudies-literature

Evi5 is required for Xenopus limb and tail regeneration.

Project description:Amphibians such as salamanders and the African clawed frog Xenopus are great models for regeneration studies because they can fully regenerate their lost organs. While axolotl can regenerate damaged organs throughout its lifetime, Xenopus has a limited regeneration capacity after metamorphosis. The ecotropic viral integrative factor 5 (Evi5) is of great interest because its expression is highly upregulated in the limb blastema of axolotls, but remains unchanged in the fibroblastema of post-metamorphic frogs. Yet, its role in regeneration-competent contexts in Xenopus has not been fully analyzed. Here we show that Evi5 is upregulated in Xenopus tadpoles after limb and tail amputation, as in axolotls. Down-regulation of Evi5 with morpholino antisense oligos (Mo) impairs limb development and limb blastema formation in Xenopus tadpoles. Mechanistically, we show that Evi5 knockdown significantly reduces proliferation of limb blastema cells and causes apoptosis, blocking the formation of regeneration blastema. RNA-sequencing analysis reveals that in addition to reduced PDGFα and TGFβ signaling pathways that are required for regeneration, evi5 Mo downregulates lysine demethylases Kdm6b and Kdm7a. And knockdown of Kdm6b or Kdm7a causes defective limb regeneration. Evi5 knockdown also impedes tail regeneration in Xenopus tadpoles and axolotl larvae, suggesting a conserved function of Evi5 in appendage regeneration. Thus, our results demonstrate that Evi5 plays a critical role in appendage regeneration in amphibians.

| S-EPMC9809974 | biostudies-literature

Notochord-derived hedgehog is essential for tail regeneration in Xenopus tadpole.

Project description:BackgroundAppendage regeneration in amphibians is regulated by the combinatorial actions of signaling molecules. The requirement of molecules secreted from specific tissues is reflected by the observation that the whole process of regeneration can be inhibited if a certain tissue is removed from the amputated stump. Interestingly, urodeles and anurans show different tissue dependencies during tail regeneration. The spinal cord is essential for tail regeneration in urodele but not in anuran larva, whereas the notochord but not the spinal cord is essential for tail regeneration in anuran tadpoles. Sonic hedgehog is one of the signaling molecules responsible for such phenomenon in axolotl, as hedgehog signaling is essential for overall tail regeneration and sonic hedgehog is exclusively expressed in the spinal cord. In order to know whether hedgehog signaling is involved in the molecular mechanism underlying the inconsistent tissue dependency for tail regeneration between anurans and urodeles, we investigated expression of hedgehog signal-related genes in the regenerating tail of Xenopus tadpole and examined the effect of the hedgehog signal inhibitor, cyclopamine, on the tail regeneration.ResultsIn Xenopus, sonic hedgehog is expressed exclusively in the notochord but not in the spinal cord of the regenerate. Overall regeneration was severely impaired in cyclopamine-treated tadpoles. Notochord maturation in the regenerate, including cell alignment and vacuolation, and myofiber formation were inhibited. Proliferation of spinal cord cells in the neural ampulla and of mesenchymal cells was also impaired.ConclusionAs in the axolotl, hedgehog signaling is required for multiple steps in tail regeneration in the Xenopus tadpole, although the location of the Shh source is quite different between the two species. This difference in Shh localization is the likely basis for the differing tissue requirement for tail regeneration between urodeles and anurans.

| S-EPMC4074850 | biostudies-literature

The AP-1 transcription factor JunB functions in Xenopus tail regeneration by positively regulating cell proliferation.

Project description:Xenopus tropicalis tadpoles can regenerate an amputated tail, including spinal cord, muscle and notochord, through cell proliferation and differentiation. However, the molecular mechanisms that regulate cell proliferation during tail regeneration are largely unknown. Here we show that JunB plays an important role in tail regeneration by regulating cell proliferation. The expression of junb is rapidly activated and sustained during tail regeneration. Knockout (KO) of junb causes a delay in tail regeneration and tissue differentiation. In junb KO tadpoles, cell proliferation is prevented before tissue differentiation. Furthermore, TGF-? signaling, which is activated just after tail amputation, regulates the induction and maintenance of junb expression. These findings demonstrate that JunB, a downstream component of TGF-? signaling, works as a positive regulator of cell proliferation during Xenopus tail regeneration.

| S-EPMC6989358 | biostudies-literature