Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell level transcriptomic anaylsis of the homeostatic and regenerating axolotl limb

ABSTRACT: Regeneration of complex multi-tissue structures, such as limbs, requires the coordinated effort of multiple cell types. In axolotl limb regeneration, the wound epidermis and blastema have been extensively studied via histology, grafting, and bulk-tissue RNA-sequencing. However, studying the contributions of these tissues is hindered due to limited information regarding the molecular identity of the cell types in regenerating limbs. By performing unbiased single-cell RNA-sequencing on over 25,000 cells from axolotl limbs, we identify a plethora of cellular diversity within epidermal, mesenchymal, and hematopoietic lineages in homeostatic and regenerating limbs. We identify regeneration-induced genes, develop putative trajectories for blastema cell differentiation, and propose the molecular identity and origin of fibroblast-derived blastema progenitor cells residing in homeostatic limbs. This work will enable application of molecular techniques to assess the contribution of these populations to limb regeneration. It will also facilitate work aimed at identifying transcripts and cells critical for limb regeneration.

ORGANISM(S): Ambystoma mexicanum

PROVIDER: GSE121737 | GEO | 2018/10/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Axolotl mandible regeneration occurs through mechanical gap closure and a shared regenerative program with the limb

Project description:The mandible plays an essential part in human life and, thus, defects in this structure can dramatically impair the quality of life in patients. Axolotls, unlike humans, are capable of regenerating their lower jaws; however, the underlying mechanisms and their similarity to those in limb regeneration are unknown. In this work, we used morphological, histological, and transcriptomic approaches to analyze the regeneration of lateral resection defects in the axolotl mandible. We found that this structure can regenerate all missing tissues in 90 days through gap minimization, blastema formation, and finally tissue growth, differentiation, and integration. Moreover, transcriptomic comparisons of regenerating mandibles and limbs showed that they share molecular phases of regeneration, that these similarities peak during blastema stages, and that mandible regeneration occurs at a slower pacing. Altogether, our study demonstrates the existence of a shared regenerative program used in two different regenerating body structures with different embryonic origins in the axolotl, and contributes to our understanding of the minimum requirements for a successful regeneration in vertebrates, bringing us closer to understand similar lesions in human mandibles.

2024-08-29 | GSE271056 | GEO

Expression data from regenerating axolotl forelimbs

Project description:Salamanders are capable of regenerating amputated limbs by generating a mass of lineage-restricted cells called a blastema. Blastemas only generate structures distal to their origin unless treated with retinoic acid (RA), which results in proximodistal (PD) limb duplications. Little is known about the transcriptional network that regulates PD duplication. In this study, we identified expression patterns that explain PD duplication including upregulation of proximal homeobox gene expression and silencing of distal-associated genes whereas limb truncation was associated with disrupted skeletal differentiation. Overall, mechanisms were identified that regulate RAR’s multifaceted roles in the salamander limb including regulation of skeletal patterning during epimorphic regeneration, skeletal tissue differentiation during regeneration, and homeostatic regeneration of intact limbs.

2017-01-10 | GSE93303 | GEO

Retinoic acid breakdown is required for proximodistal positional identity during axolotl limb regeneration

Project description:Regenerating limbs retain their proximodistal (PD) positional identity following amputation. This positional identity is encoded genetically by PD patterning genes, which instruct blastema cells to regenerate the appropriate PD limb segment. Retinoic acid (RA) is known to specify proximal limb identity, but how RA concentration is established in the blastema is unknown. Here, we show that RA breakdown via CYP26B1 is essential for determining the RA concentration within blastemas. CYP26B1 inhibition molecularly reprograms distal blastemas into a proximal identity, phenocopying the effects of administering excess RA. We identify Shox as an RA responsive gene that is differentially expressed between proximally and distally amputated blastemas. Ablation of Shox results in shortened limbs with proximal skeletal elements that fail to undergo endochondral ossification. These results suggest that PD positional identity is determined by RA degradation and that targets of RA have a critical role in skeletal element formation during limb regeneration.

2024-07-22 | GSE272731 | GEO

Gene expression of senescent and non-senescent AL1 cells

Project description:Axolotl limb regeneration proceeds through the formation of a blastema, a mound of progenitor cells that accumulate at the end of the amputated stump. These progenitor cells expand and later undergo patterning to regenerate the missing limb, restoring both form and function. A subset of cells within the blastema become senescent, a state of permanent growth arrest. Here, we address the functional relevance of cellular senescence to axolotl limb regeneration, through a combination of gain- and loss-of-function assays. Using transcriptomic analyses on in vitro and in vivo senescent cells, we gain insights into the basis of the senescent phenotype, cell-cycle arrest, and molecular mediators involved in axolotl regeneration at the molecular level.

2023-07-10 | GSE206237 | GEO

Single-cell RNA profiling of blastemal senescent cells

2023-07-10 | GSE206235 | GEO

Gene expression profile of senescent and non-senescent cells from regenerating blastemas

2023-07-10 | GSE206234 | GEO

Comparative Transcriptional Profiling of the Axolotl Limb Identifies a Tripartite Regeneration-Specific Gene Program

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

Blastemal progenitors modulate immune signaling during early limb regeneration.

Project description:Blastema formation is a hallmark of limb regeneration that requires proliferation and migration of progenitors derived from many tissues to the amputation plane. To better understand the genetic programs that initiate limb regeneration, we reasoned that blastemal progenitors would be among early proliferating cells in the stump following amputation. Here we separately profiled dividing and non-dividing stump tissues, as well as the wound epidermis, during early axolotl limb regeneration to examine transcriptional programs of blastemal progenitors. We provide a description of the changes in gene expression specific to early dividing cells at the site of amputation, inclusive of progenitors for the regenerating limb. This work collectively demonstrates differential suppression/activation of core developmental signaling pathways in subsets of the early regenerating limb and further suggests that interleukin-8 (il-8) signaling is important for regeneration.

2019-01-01 | GSE111213 | GEO

Comparative Transcriptional Profiling of the Axolotl Limb Identifies a Tripartite Regeneration-Specific Gene Program

2013-01-01 | GSE36451 | GEO