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Progressive cell fate specification in morphallactic regeneration [scRNA-seq]

ABSTRACT: Through regeneration variable species replace lost parts of their body. This is achieved either by growth of new structures at the amputation side (epimorphosis), as is the case of axolotl limb regeneration, or through remodeling of the remaining tissue (morphallaxis), as happens in Hydra. Whereas work on epimorphic regeneration support a gradual proximal to distal establishment of cell identities, morphallactic regeneration is believed to rely on initial establishment of boundary conditions that organize the adjustment of the pattern. Performing single cell RNA sequencing during regeneration in Hydra, we revealed the sequence of cells’ transdifferentiation into the missing identities. We provide evidence that morphallaxis proceeds with progressive specification of cell fates, unifying its mechanism with the one found for epimorphosis.

ORGANISM(S): Hydra vulgaris

PROVIDER: GSE300723 | GEO | 2026/04/28

REPOSITORIES: GEO

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Progressive cell fate specification in morphallactic regeneration [RNA-seq]

Project description:Through regeneration variable species replace lost parts of their body. This is achieved either by growth of new structures at the amputation side (epimorphosis), as is the case of axolotl limb regeneration, or through remodeling of the remaining tissue (morphallaxis), as happens in Hydra. Whereas work on epimorphic regeneration support a gradual proximal to distal establishment of cell identities, morphallactic regeneration is believed to rely on initial establishment of boundary conditions that organize the adjustment of the pattern. Performing single cell RNA sequencing during regeneration in Hydra, we revealed the sequence of cells’ transdifferentiation into the missing identities. We provide evidence that morphallaxis proceeds with progressive specification of cell fates, unifying its mechanism with the one found for epimorphosis.

2026-04-28 | GSE300721 | GEO

Small RNA and mRNA expression profiling during axolotl forelimb regeneration

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

Three Distinct Phases of Regeneration-Specific Gene Expression in the Axolotl Blastema

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

Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming

Project description:The axolotl (<i>Ambystoma mexicanum</i>) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some extent, the metabolic changes experienced and their associated implications, remain unexplored. However, a circuit with a potential role as a modulator of cellular metabolism along regeneration is that formed by Lin28/let-7. In this study, we report two Lin28 paralogs and eight mature let-7 microRNAs encoded in the axolotl genome. Particularly, in the proliferative blastema stage amxLin28B is more abundant in the nuclei of blastemal cells, while the microRNAs amx-let-7c and amx-let-7a are most downregulated. Functional inhibition of Lin28 factors increase the levels of most mature let-7 microRNAs, consistent with an increment of intermediary metabolites of the Krebs cycle, and phenotypic alterations in the outgrowth of the blastema. In summary, we describe the primary components of the Lin28/let-7 circuit and their function during axolotl regeneration, acting upstream of metabolic reprogramming events.

2021-11-04 | MTBLS1708 | MetaboLights

Single cell RNA sequencing of adult regenerating mouse digit tips

Project description:Innate regeneration following digit tip amputation is one of the few examples of epimorphic regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses in mice, the digit tip blastema has been defined as a population of heterogeneous, lineage restructed progenitor cells. These previous studies, however, do not comprehensively evaluate blastema heterogeneity or address lineage restruction of closely related cell types. Here we report one additional single cell RNA sequencing sample (28 days post-amputation) to add to our already published 38,000 cells from mouse digit tip blastemas and unamputated control digit tips used to generate an atlas of the cell types participating in digit tip regeneration.

2024-07-03 | GSE267446 | GEO

Transcription profiling of zebrafish adult and larval fin to investigate mechanisms of regeneration

Project description:Zebrafish have the remarkable ability to regenerate body parts including the heart, spinal cord and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage-larvae also possess the ability to regenerate the caudal fin. A comparative genomic analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart and larval fin. Results indicate that these tissues respond to amputation/injury with strikingly similar genomic responses. Comparative analysis revealed raldh2, a rate-limiting enzyme for the synthesis of Retinoic acid (RA), as one of the highly induced genes across the three regeneration platforms. Experiment Overall Design: The caudal fin of zebrafish larvae at 2days post fertilization were amputated. Caudal fin tissue at 2dpf and regenerating fins were isolated at 1, 2and 3 days post amputation. Three replicates were collected at each time point. 150 fins were pooled to comprise one replicate.

2008-04-07 | E-GEOD-10188 | biostudies-arrayexpress

Molecular basis of positional memory in limb regeneration [RNA-seq]

Project description:Amputation of a salamander limb triggers anterior and posterior connective tissue cells to form distinct signalling centres that together fuel regeneration. Anterior and posterior identities are established during development and are thought to persist lifelong in the form of positional memory. However, neither the molecular basis of positional memory nor whether positional memory can be altered is known. Here, we identify a positive feedback loop responsible for posterior identity in the axolotl (Ambystoma mexicanum) limb. Posterior cells express residual Hand2 transcription factor from development, which primes them to form a Shh signalling centre after limb amputation. During regeneration, Shh signalling is also upstream of Hand2 expression. After regeneration, Shh is shut down but Hand2 is sustained, safeguarding posterior memory. We exploited this regeneration circuitry to convert anterior cells to a posterior cell memory state. Transient exposure of anterior cells to Shh during regeneration kick-started an ectopic Hand2-Shh loop, leading to stable Hand2 expression and a lasting competence to express Shh. Our results implicate positive feedback in the stability of positional memory and reveal that positional memory is more easily reprogrammed in one direction (anterior to posterior) than the other. Modifying positional memory in regenerative cells changes their signalling outputs, which has implications for tissue engineering.

2025-03-21 | GSE284768 | GEO

Molecular basis of positional memory in limb regeneration [RNA-seq]

2025-03-21 | GSE243137 | GEO

Genome-wide maps RNA Polymerase II and Histone H3 of Hydra vulgaris

Project description:Hydra have a remarkable ability to regenerate after bisection or dissociation. Thus, Hydra is a unique model for studying the mechanisms underlying stemness and self renewal biology. The regeneration of Hyrda offers unique way to investigate molecular mechanisms leading to the establishment of organizer activity during animal development. Here we have investigated the genome-wide occurrence of RNA Polymearse II and Histone H3 in Hydra vulgaris.

2020-01-01 | GSE63414 | GEO

Gene Expression During the First 28 Days of Axolotl Limb Regeneration

Project description:Here we report the results of a robust microarray experiment that examined the first 28 days of axolotl forelimb regeneration. At each of 20 post-amputation time points, we estimated gene expression for 10 replicate RNA samples that were isolated from 1m of heterogeneous tissue collected from the distal limb tip.

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