The axolotl kidney: a novel model to study kidney regeneration
Ontology highlight
ABSTRACT:
ORGANISM(S): Ambystoma mexicanum
PROVIDER: GSE228583 | GEO | 2023/10/10
REPOSITORIES: GEO
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Project description:Humans and other tetrapods are considered to require apical-ectodermal-ridge, AER, cells for limb development, and AER-like cells are suggested to be re-formed to initiate limb regeneration. Paradoxically, the presence of AER in the axolotl, the primary regeneration model organism, remains controversial. Here, by leveraging a single-cell transcriptomics-based multi-species atlas, composed of axolotl, human, mouse, chicken, and frog cells, we first established that axolotls contain cells with AER characteristics. Surprisingly, further analyses and spatial transcriptomics revealed that axolotl limbs do not fully re-form AER cells during regeneration. Moreover, the axolotl mesoderm displays part of the AER machinery, revealing a novel program for limb (re)growth. These results clarify the debate about the axolotl AER and the extent to which the limb developmental program is recapitulated during regeneration.
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Project description:Salamanders have the remarkable ability to functionally regenerate after spinal cord transection. In response to injury, GFAP+ glial cells in the axolotl spinal cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon regeneration. Molecular pathways that regulate the pro-regenerative axolotl glial cell response are poorly understood. Here we show axolotl glial cells up-regulate AP-1cFos/JunB after injury, which promotes a pro-regenerative glial cell response. Axolotl glial cells directly repress c-Jun expression via up-regulation of miR-200a. Inhibition of miR-200a during regeneration causes defects in axonal regrowth and transcriptomic analysis revealed that miR-200a inhibition leads to differential regulation of genes involved with reactive gliosis, the glial scar, ECM remodeling and axon guidance. This work identifies a novel role for miR-200a in inhibiting reactive gliosis in glial cell in axolotl during spinal cord regeneration
2019-03-19 | GSE122939 | GEO
Project description:Identifying the genetic program that induces limb regeneration in salamanders is an important resource for regenerative medicine, which currently lacks tools to promote regeneration of functional body structures. The genetic network underlying limb regeneration has been elusive due to the complexity of the injury response that occurs concomitant to blastema formation. Here we performed parallel expression profile time courses of non-regenerative lateral wounds versus amputated limbs in axolotl. We show that limb regeneration occurs in three distinguishable phases--early wound healing followed by a transition phase leading to establishment of the limb development program. By focusing on the transition phase, we identified 93 strictly regeneration-associated genes involved in oxidative stress response, chromatin modification, epithelial development and limb development. The specific expression of the genes was confirmed by in situ hybridization. Regeneration-specific expression databases are critical resources for understanding how regeneration-relevant phenotypes can be induced from adult cells Regeneration of the axolotl forelimb lower arm was compared with the healing of a deep lateral injury in a high density timecourse (uncut, 3h, 6h, 9h, 12h, 24h, 36h, 52h, 72h, 120h, 168h, 288h and 528h after injury). Three independent biological replicates were performed using separate cluches of animals. Amputated and lateral wound samples were made as matched contralateral samples of four pooled animals per timepoint.
2013-01-01 | E-GEOD-36451 | biostudies-arrayexpress
Project description:The Mexican axolotl (Ambystoma mexicanum) is one member of a select group of vertebrate animals that has retained the amazing ability to regenerate multiple body parts. In addition to being an important model system for regeneration, the axolotl is also a leading model system for developmental biologists. Many genes used in development have been identified to be reused again during regeneration, however how this molecular circuitry is controlled during regeneration is unknown. In recent years microRNAs have been identified as key regulators of gene expression during development, in many diseases and also in regeneration. Here we have used deep sequencing combined with qRT-PCR to identify microRNAs that are involved in regulating regeneration in axolotl. This approach has enabled us to identify well known families of microRNAs and in addition to identify putative novel microRNAs that differentially regulated in the regenerating tissue. These findings suggest that microRNAs may play key roles in managing the spatial and temporal expression of genes important for ensuring that the correct tissues are regenerated. small RNA Sequencing (2 samples) in Ambystoma Mexicanum
2015-09-11 | E-GEOD-72057 | biostudies-arrayexpress
Project description:We sequenced the transcriptome of gentamicin induced renal regeneration in adult zebrafish. Specifically, zebrafish kidney tissues in the first, third, fifth and seventh days of kidney injury and the control group were selected. Each sample contains three kidneys. Three samples were taken in each period, and then the total RNA of the kidney was extracted for second-generation sequencing.
2021-12-19 | GSE191068 | GEO
Project description:Endogenous bioelectric signaling via changes in cellular resting potential (Vmem) is a key regulator of patterning during regeneration and embryogenesis in numerous model systems. Depolarization of Vmem has been functionally implicated in de-differentiation, tumorigenesis, anatomical re-specification, and appendage regeneration. However, no unbiased analyses have been performed to understand genome-wide transcriptional responses to Vmem change in vivo. Moreover, it is unknown which genes or gene networks represent conserved targets of bioelectrical signaling across different patterning contexts and species. Here, we use microarray analysis to comparatively analyze transcriptional responses to specific Vmem depolarization. We compare the response of the transcriptome during embryogenesis (Xenopus development), regeneration (Axolotl regeneration), and stem cell differentiation (human mesenchymal stem cells in culture) to identify common networks across model species that are associated with depolarization. Both sub-network enrichment and PANTHER analyses identified a number of key genetic modules as targets of Vmem change, and also revealed important (well-conserved) commonalities in bioelectric signal transduction, despite highly diverse experimental contexts and species. Depolarization regulates specific transcriptional networks across all three germ layers (ectoderm, mesoderm and endoderm) such as cell differentiation and apoptosis, and this information will be used for developing mechanistic models of bioelectric regulation of patterning. Moreover, our analysis reveals that Vmem change regulates transcripts related to important disease pathways such as cancer and neurodegeneration, which may represent novel targets for emerging electroceutical therapies. All axolotls used in these experiments were bred in the axolotl facility at the University of Minnesota under the IACUC protocol #1201A08381. Axolotls of 2â3 cm were used for all in vivo experiments, and animals were kept in separate containers and fed daily with artemia; water was changed daily. Animals were anesthetized in 0.01% p-amino benzocaine (Sigma) before microinjection was performed. There were 9 microarrays conducted, and these were ivermectin-treated (n=3). Experimental Design: Ivermectin injection Ivermectin or vehicle only (water) was pressure injected into the central canal of the spinal cord, and this was visualized by the addition of Fast Green into the solution. Directly after injection, a portion of the spinal cord was surgically removed and the animals were placed back into water in individual containers. One day post injury (1dpi) animals were anesthetized again and the area of the injury was removed. Tissue from 10 animals were pooled for each microarray replicate. Mature - Uninjured spinal cord tissue Sc Crush- spinal cord tissue 1 day after injury Ivermectin - Ivermectin injected spinal cord tissue 1 day after injury.
2016-07-03 | E-GEOD-72096 | biostudies-arrayexpress
Project description:Previous studies of appendage regeneration in the axolotl have shown that multiple genetic programs are modulated through regulatory factors. MicroRNAs are short highly conserved non-coding genes that suppress expression of target genes and thereby control multiple genetic programs. Given their important regulatory roles and evolutionary conservation, we hypothesize that microRNAs define a conserved genetic regulatory circuit important for appendage regeneration. We characterized microRNA expression during Axolotl forelimb regeneration using small RNA sequencing. The same samples were assayed for mRNA expression using mRNA sequencing. Small RNA and mRNA gene expression profiling during 0, 3, 6 and 14 days post amputation.
2016-06-01 | E-GEOD-74372 | biostudies-arrayexpress
Project description:The Mexican axolotl (Ambystoma mexicanum) is one member of a select group of vertebrate animals that has retained the amazing ability to regenerate multiple body parts. In addition to being an important model system for regeneration, the axolotl is also a leading model system for developmental biologists. Many genes used in development have been identified to be reused again during regeneration, however how this molecular circuitry is controlled during regeneration is unknown. In recent years microRNAs have been identified as key regulators of gene expression during development, in many diseases and also in regeneration. Here we have used deep sequencing combined with qRT-PCR to identify microRNAs that are involved in regulating regeneration in axolotl. This approach has enabled us to identify well known families of microRNAs and in addition to identify putative novel microRNAs that differentially regulated in the regenerating tissue. These findings suggest that microRNAs may play key roles in managing the spatial and temporal expression of genes important for ensuring that the correct tissues are regenerated.
2015-09-11 | GSE72057 | GEO
Project description:The salamander has the remarkable ability to regenerate its limb after amputation. Cells at the site of amputation form a blastema and then proliferate and differentiate to regrow the limb. To better understand this process, we have performed deep RNA sequencing of the blastema over a time course. We find genes expressed in three phases with a prominent burst in oncogene expression during the first day, blastemal/limb bud genes peaking at 7 to 14 days, and markers for terminal differentiation upregulated later. We compare these expression patterns to those in a mouse digit amputation model to identify genes specific to the regenerative response. We find that limb patterning genes, SALL genes, and genes involved in the proteasome, adult stem cell, embryonic stem cell, retinoid metabolism, and WNT and NOTCH signaling are regeneration-specific. We establish the “Axolomics” Database, which provides a tool for depositing, retrieving, and searching axolotl-related “omic” information. The experiment includes two time course data sets. One is from mouse digit amputation, another is from Axolotl digit amputation
2013-09-01 | E-GEOD-34394 | biostudies-arrayexpress
Project description:We adopted a combinatorial hybridization based single-cell RNA-seq method to generate tissue based transcriptome atlas of adult axolotl and whole organism transcriptome atlas of larva axolotl. Gene expression profiling of over 1million single cells across 19 organs constructed the first adult axolotl cell atlas. Comparison between neoteny and metamorphosis organs revealed transcriptome heterogeneity of structural cells in different tissues and a sophisticated regulatory network. Furthermore, we described dynamic gene expression pattern during neotenic larva axolotl limb development. These data serve as a rich resource to explore molecular identity of axolotl as well as its metamorphosis.
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