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Spatial transcriptomics reveals increased energetic requirements underpinning age-dependent declines in digit regeneration rescued through administration of OAA

ABSTRACT: Spatial transcriptomics reveals increased energetic requirements underpinning age-dependent declines in digit regeneration rescued through administration of OAA

PROVIDER: PRJNA749116 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15219637.fastq.gz	Fastqsanger.gz
	SRR15219638.fastq.gz	Fastqsanger.gz
	SRR15219639.fastq.gz	Fastqsanger.gz
	SRR15219640.fastq.gz	Fastqsanger.gz
	SRR17993064_1.fastq.gz	Fastqsanger.gz

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Spatial transcriptomics reveals increased energetic requirements underpinning age-dependent declines in digit regeneration rescued through administration of OAA

Project description:De novo limb regeneration after amputation is restricted in mammals to the distal digit tip. Central to this regenerative process is the blastema, a heterogeneous population of lineage-restricted, dedifferentiated cells that ultimately orchestrates the regeneration of the amputated bone and surrounding soft tissue. To investigate skeletal regeneration, we made use of spatial transcriptomics to characterize the transcriptional profile specifically within the blastema. Using this technique, we generated a gene signature with high specificity for the blastema in both our spatial data, as well as other previously published single-cell RNA-sequencing transcriptomic studies. To elucidate potential mechanisms distinguishing regenerative from non-regenerative healing, we applied spatial transcriptomics to an aging model. Consistent with other forms of repair, our digit amputation mouse model showed a significant impairment in regeneration in aged mice. Contrasting young and aged mice, spatial analysis revealed a metabolic shift in aged blastema associated with an increased bioenergetic requirement. This enhanced metabolic turnover was associated with increased hypoxia and angiogenic signaling, leading to excessive vascularization and altered regenerated bone architecture in aged mice. Restoration of this metabolic deficiency using the metabolite oxaloacetate enhanced in vivo bone regeneration. Thus, targeting cell metabolism may be a promising strategy to mitigate aging-induced declines in tissue regeneration.

2022-06-01 | GSE180682 | GEO

Nerve-derived Schwann cell precursors, acting in a paracrine fashion, are essential for mammalian digit tip regeneration [RAT]

Project description:Multi-tissue regenerative capacity is lost in adult mammals with the exception of the distal digit, which regenerates via largely-uncharacterized mechanisms. Here, we demonstrate that following adult mouse distal digit removal, nerve-associated Schwann cell precursors (N-SCPs) dedifferentiate and secrete growth factors that promote expansion of the blastema and digit regeneration. Specifically, when N-SCPs were dysregulated or ablated, mesenchymal precursor proliferation in the blastema was decreased, nail and bone regeneration were impaired, and regeneration could be rescued by transplantation of exogenous N-SCPs. We show that N-SCPs secreted factors that promoted self-renewal of mesenchymal precursors, and we used transcriptomic and proteomic analysis to define candidate factors. Two of these, oncostatin M (OSM) and PDGF-AA, were made by N-SCPs in the regenerating digit, and rescued the deficits in regeneration caused by loss of N-SCPs due to denervation. Since nerves innervate every peripheral tissue, these results have broad implications for mammalian tissue repair and regeneration.

2016-07-12 | GSE81703 | GEO

Nerve-derived Schwann cell precursors, acting in a paracrine fashion, are essential for mammalian digit tip regeneration [MOUSE]

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Foxo signaling declines with age

Project description:Foxo signaling declines with age

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Digital gene expression tag profiling of digit morphologies in bats

Project description:As the only truly flying mammals, bats use their unique wing formed from elongated digits connected by membranes to power their flight. The forelimb of bats consists of four elongated digits (digits II-V) and one shorter digit (digit I) that is morphologically similar to the hindlimb digits. Elongation of bat forelimb digits is thought to results from changes in the temporal and spatial expression of a number of developmental genes. As a result, comparing gene expression profiles between short and elongated digit morphologies of the fore- and hindlimbs may elucidate the molecular mechanisms underlying digit elongation in bats. Here, we performed a large-scale analysis of gene expression of forelimb digit I, forelimb digits II-V, and all five hindlimb digits in Myotis ricketti using digital gene expression tag profiling approach. Results of this study not only implicate several developmental genes as robust candidates underlying digit elongation in bats, but also provide a better understanding of the genes involved in autopodial development in general. A large-scale analysis of gene expression of 3 different parts of autopods in Myotis ricketti using digital gene expression tag profiling approach.

2010-12-06 | E-GEOD-20038 | biostudies-arrayexpress

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 single cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and unamputated control digit tips and generate an atlas of the cell types participating in digit tip regeneration.

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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

Digital gene expression tag profiling of digit morphologies in bats

2010-12-06 | GSE20038 | GEO

Expression data of e13.5 Sox-GFP forming digit, e14.5 Lgr5-GFP+ interzone and e14.5 GFP- surrounding tissues in digit

Project description:Lgr5 is a novel marker expressing in the interzone from around e14.5 of developing synovial joint. By comparing the expression profiles of e14.5 Lgr5+ interzone cells, surrounding Lgr5- non-interzone cells and also e13.5 digit, we have identified some differential expressing genes in the interzone. We have generated bulk RNAseq data of e14.5 Lgr5+ interzone cells, surrounding non-interzone cells and e13.5 Sox9+ chondrocytes cells in digit.

2018-02-08 | GSE110281 | GEO

Foxo signaling declines with age

Project description:We performed RNA-seq for WT and foxo mutant flies, by combining with Dr. Baihua's foxo chip-seq data, we found 101 foxo-repressed and 300 foxo-activated genes. By analyzing expression change of these genes during age, we found foxo-repressed genes became activated, while foxo-activated genes became repressed, suggesting foxo signaling declines with age.

2018-11-14 | GSE122470 | GEO

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