Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration.
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ABSTRACT:
PROVIDER: PRJNA1082368 | ENA |
REPOSITORIES: ENA
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Project description:Injury is a common occurrence in the life of most if not all organisms. Because injury and the extent of damage inflicted are not predictable events, pre-existing tissues must somehow determine how much tissue needs to be restored. It has been known for over a century that amputation position along a proximal-distal (P/D) axis determines the regeneration speed of amputated limbs in regeneration-competent animals1. Yet, it is not clear how an injured limb conveys positional information during regeneration to faithfully restore pre-existing morphologies and functions. Here, we profiled millimetric caudal fins regenerating proximal and distal amputations in the African killifish (Nothobranchius furzeri). We report position-specific, differential modulation of the spatial distribution, duration, and magnitude of proliferation, and the possibility to predict blastema sizes. Regenerating fins profiled by single cell RNA sequencing identified a Transient Regeneration-Activated Cell State (TRACS) enriched in extracellular matrix (ECM) components and modifiers that is proportionally amplified to match a given amputation position. We located this transient cell state to the basal epidermis by gene expression and confocal microscopy, and propose a role for these cells in transducing positional information to the regeneration blastema. Understanding the temporal deployment of regenerative cell states may hold the key to set up a successful regeneration event in organisms with limited regenerative abilities such as humans.
2024-04-01 | GSE260629 | GEO
Project description:Regeneration requires cells to regulate proliferation and patterning according to their spatial position. Positional memory is a property that enables regenerating cells to recall spatial information from the uninjured tissue. Positional memory is hypothesized to rely on gradients of molecules, few of which have been identified. Here, we quantified the global abundance of transcripts, proteins and metabolites along the proximodistal axis of caudal fins of uninjured and regenerating adult zebrafish. Using this approach, we uncovered complex overlapping expression patterns for hundreds of molecules involved in diverse cellular functions, including developmental and bioelectric signaling as well as amino acid and lipid metabolism. Moreover, 32 genes differentially expressed at the RNA level had concomitant differential expression of the encoded proteins. Thus, the identification of proximodistal differences in levels of RNAs, proteins, and metabolites will facilitate future functional studies of positional memory during appendage regeneration.
2017-01-21 | GSE92760 | GEO
Project description:Species within nearly all extant animal lineages are capable of regenerating body parts. However, it remains unclear whether the gene expression programme controlling regeneration is evolutionarily conserved. Brittle stars are a species-rich class of echinoderms with outstanding regenerative abilities, but investigations into the genetic bases of regeneration in this group have been hindered by the limited available genomic resources. Here, we report a chromosome-scale genome assembly for the brittle star Amphiura filiformis. We show that the brittle star displays the most rearranged genome amongst echinoderms sequenced to date, featuring a reorganised Hox cluster reminiscent of the rearrangements observed in sea urchins. In addition, we performed an extensive profiling of gene expression throughout brittle star adult arm regeneration and identified sequential waves of gene expression governing wound healing, proliferation and differentiation. We conducted comparative transcriptomic analyses with other invertebrate and vertebrate models for appendage regeneration and uncovered hundreds of genes with conserved expression dynamics, notably during the proliferative phase of regeneration. Our findings emphasise the crucial importance of echinoderms to detect long-range expression conservation between vertebrates and classical invertebrate regeneration model systems.
2024-05-07 | GSE246675 | GEO
Project description:Previous studies of vertebrate appendage regeneration have shown that multiple genetic programs are moduled 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 Polypterus senegalus (bichir) pectoral fin 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, 7 and 14 days post amputation.
2016-06-01 | E-GEOD-74374 | biostudies-arrayexpress
Project description:We know little about the control of positional information (PI) during axolotl limb regeneration which ensures that the limb regenerates exactly what was amputated and the work reported here investigates this phenomenon. Retinoic acid administration changes the PI in a proximal direction so that a complete limb can be regenerated from a hand. Rather that identifying all the genes altered by RA treatment of the limb, we have eliminated many off-target effects by using retinoic acid receptor selective agonists. We firstly identify the receptor involved in this respecification process as RARα and secondly identify the genes involved by RNA sequencing of the RARα-treated blastemal mesenchyme. We find 1177 up-regulated genes and 1403 down-regulated genes which could be identified using the axolotl genome. These include several genes known to be involved in retinoic acid metabolism and in patterning. Since positional in-formation is thought to be a property of the cell surface of blastemal cells when we examine our dataset with an emphasis on this aspect, we find the top canonical pathway is integrin signaling. In the extracellular matrix compartment, we find an MMP and several collagens are up-regulated and several cell membrane genes and secretory factors are also up-regulated. This provides data for future testing of the function of these candidates in the control of PI during limb regeneration.
2021-08-20 | GSE182296 | GEO
Project description:Previous studies of vertebrate appendage regeneration have shown that multiple genetic programs are moduled 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 Polypterus senegalus (bichir) pectoral fin regeneration using small RNA sequencing. The same samples were assayed for mRNA expression using mRNA sequencing.
2016-06-01 | GSE74374 | GEO
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
Project description:Retinoic acid receptors and the control of positional information in the regenerating axolotl limb
| PRJNA755711 | ENA
Project description:The brittle star genome illuminates the genetic basis of animal appendage regeneration
| PRJNA1034116 | ENA
Project description:The salamander limb regenerates only the missing portion. Each limb segment can only form segments equivalent to- or more distal to their own identity, relying on a property termed “positional information”. How positional information is encoded in limb cells has been unknown. By cell-type-specific chromatin profiling of upper arm, lower arm, and hand, we found segment-specific levels of histone H3K27me3 at limb homeoprotein gene loci but not their upstream regulators, constituting an intrinsic segment information code. During regeneration, regeneration-specific regulatory elements became active prior to the re-appearance of developmental regulatory elements. This means that, in the hand segment, the permissive chromatin state of the hand homeoprotein gene HoxA13 engages with regeneration regulatory elements, bypassing the upper limb program. Profiling chromatin accessibility (ACRs) of Axoltol limb connective tissue cells, and compare among developmental limb buds, and mature limb at different segments and regeneration time points.
2023-04-10 | GSE217592 | GEO