Control of osteoblast regeneration by a train of Erk activity waves
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA615232 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We report here a dataset regarding the transcriptome of Erk active osteoblasts in regenerating zebrafish scales. We recently discovered that the marker osx:Venus-hGeminin anti-correlates with Erk activity in those cells. Thus, by sorting (using FACS) cells based on both the expression of an osteoblast marker (osx::H2A-mCherry) and the levels of hGeminin, we could sort osteoblasts into separate Erk+ and Erk- populations and perform RNAsequence (in triplicates). We found that dusp and sprouty transcripts are elevated in osteoblasts with high Erk activity. Specifically, dusp2, dusp5 and spry4 transcripts are predominant in scales and consistently present at higher levels in the population enriched for Erk+ cells.
2020-09-23 | GSE147551 | GEO
Project description: Not available
| S-EPMC7864885 | biostudies-literature
Project description:Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Currently, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate ERK activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained at high levels during complex tissue regeneration. Following ERK inhibition, ear punch regeneration in Acomys shifted towards fibrotic repair. Using scRNA-seq, we identified ERK-responsive cell types. Loss- and gain-of-function experiments prompted us to uncover FGF and ErbB signaling as upstream ERK regulators of regeneration. Strikingly, the ectopic activation of ERK in scar-prone injuries induced a pro-regenerative response, including cell proliferation, extracellular matrix remodeling and hair follicle neogenesis. Our data detail an important distinction in ERK activity between regenerating and poorly regenerating adult mammals and open avenues to redirect fibrotic repair towards regenerative healing.
2023-04-28 | GSE224879 | GEO
Project description:Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Currently, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate ERK activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained during complex tissue regeneration. Following ERK inhibition, regeneration in Acomys shifted towards a fibrotic repair. Using scRNA-seq, we uncovered that MAPK/ERK signaling acts in a cell type specific manner to direct regenerative healing. Loss- and gain-of-function experiments prompted us to identify FGF and ErbB signaling as upstream ERK regulators of regeneration. By ectopically activating ERK in Mus injuries, a pro- regenerative response was induced, including cell proliferation, extracellular matrix remodeling and hair follicle neogenesis. Our data provide new insights into why some mammals regenerate better than others and open avenues to redirect fibrotic repair towards regenerative healing.
2023-04-28 | GSE224433 | GEO
Project description:Human adult mesenchymal stromal cells (hMSC) have the potential to differentiate into chondrogenic, adipogenic or osteogenic lineages, providing a potential source for tissue regeneration. An important issue for efficient bone regeneration is to identify factors that can be targeted to promote the osteogenic potential of hMSCs. Using transcriptomic analysis, we found that integrin alpha5 (ITGA5) expression is upregulated during dexamethasone-induced hMSCs osteoblast differentiation. Gain-of-function studies showed that ITGA5 promotes the expression of osteoblast phenotypic markers as well as in vitro osteogenesis in hMSCs. Downregulation of endogenous ITGA5 using shRNA blunted osteoblast marker expression and osteogenic differentiation. Pharmacological and molecular analyses showed that the enhanced hMSCs osteoblast differentiation induced by ITGA5 was mediated by activation of FAK/ERK1/2-MAPKs and PI3K signaling pathways. Remarkably, activation of ITGA5 using a specific antibody that primes the integrin or a peptide that specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K signaling and to promote osteoblast differentiation and osteogenic capacity of hMSCs. We also demonstrate that hMSCs engineered to over-express ITGA5 exhibited a marked increase in their osteogenic potential in vivo. These findings not only reveal that ITGA5 is required for osteoblast differentiation of adult human MSCs but also provide a novel targeted strategy using ITGA5 agonists to promote the osteogenic capacity of hMSCs, which may be used for tissue regeneration in bone disorders where the recruitment or capacity of MSCs is compromised. Keywords: Time course of osteogenic differentiation processes
2009-09-10 | GSE18043 | GEO
Project description:SORLA is a type I transmembrane component associated with Alzheimers disease (AD) risk. Although SORLA is abundantly expressed in neurons, physiological roles for SORLA remain yet unclear. Here, we show that cultured neurons overexpressing SORLA (SORLA TG) feature enhanced neurite length, and accelerated neurite regeneration with wounding. Enhanced accumulation of a soluble SORLA form (sSORLA) is observed in SORLA TG neurons, where purified sSORLA can sufficiently drive neurite extension and regeneration. Phosphoproteomic analysis indicates enrichment of phosphoproteins related to the EGFR/ERK pathway in SORLA TG hippocampus. We find that sSORLA can co-precipitate with EGFR in vitro, where sSORLA treatment can induce EGFR Y1173 phosphorylation in cultured neurons. sSORLA also triggers Erk activation and downstream c-fos upregulation/nuclear translocation, where pharmacological EGFR or ERK inhibition reversed enhancements in sSORLA-dependent neurite regeneration. Together, these results implicate the EGFR as a sSORLA receptor which activates ERK/c-Fos pathways to enhance neurite extension, outgrowth and regeneration.
2020-05-12 | MSV000085400 | MassIVE
Project description:Shock waves induce an evolutionary conserved mechanism of spinal cord regeneration via Toll-like receptor 3
| PRJNA628694 | ENA
Project description:Global expression profile of human osteoblast treated with melphalen, compared to human osteoblast cells treated with diluent control
2010-09-30 | GSE17839 | GEO
Project description:Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling
2009-04-02 | E-TABM-626 | biostudies-arrayexpress