Single-cell RNA-seq - Jmj KO, Utx KO, Tdt.Control
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE186787 | GEO | 2022/08/04
REPOSITORIES: GEO
Similar Datasets
Project description:Stem cells reside in specialized niches that play a critical role in modulating their fate. It remains unknown how MuSC adapt to the modified milieu to mediate muscle repair. Here, we show that the epigenetic enzyme JMJD3 coordinates MuSC adaptation to the regenerative niche in a non-cell autonomous manner where it modifies their extracellular matrix to integrate signaling that stimulates exit of quiescence. Genomics and transcriptomics approaches identified the hyaluronic acid (HA) synthesis enzyme Has2 as a key JMJD3 target gene that allows MuSCs to integrate signals from the regenerative niche.
2022-08-04 | GSE186786 | GEO
Project description:Stem cells reside in specialized niches that play a critical role in modulating their fate. Supporting cells in the niche instruct fate changes to the stem cells through epigenetic enzymes that transduce cell signaling to modify gene expression. Recent studies showed that the innate immune response to muscle injury alters the muscle stem cell (MuSC) niche, it remains unknown how MuSC adapt to the modified milieu to mediate muscle repair. Here we show that the epigenetic enzyme JMJD3 coordinates MuSC adaptation to the regenerative niche in a non-cell autonomous manner where it modifies their extracellular matrix to integrate signaling that stimulates exit of quiescence. Genomics and transcriptomics approaches identified the hyaluronic acid (HA) synthesis enzyme Has2 as a key JMJD3 target gene that allows MuSCs to integrate signals from the regenerative niche. Overall, we identified a specific role for JMJD3 in regulating the expression of genes that allow MuSCs to adapt to the modified niche of regenerating muscle. We aim to determine the differential occupancy of histone H3 lysine 4 trimethyl mark muscle satellite stem cells isolated from JMJD3scKO, UTXscKO and Wild-type mice.
2022-08-04 | GSE186830 | GEO
Project description:Stem cells reside in specialized niches that play a critical role in modulating their fate. Supporting cells in the niche instruct fate changes to the stem cells through epigenetic enzymes that transduce cell signaling to modify gene expression. Recent studies showed that the innate immune response to muscle injury alters the muscle stem cell (MuSC) niche, it remains unknown how MuSC adapt to the modified milieu to mediate muscle repair. Here we show that the epigenetic enzyme JMJD3 coordinates MuSC adaptation to the regenerative niche in a non-cell autonomous manner where it modifies their extracellular matrix to integrate signaling that stimulates exit of quiescence. Genomics and transcriptomics approaches identified the hyaluronic acid (HA) synthesis enzyme Has2 as a key JMJD3 target gene that allows MuSCs to integrate signals from the regenerative niche. Overall, we identified a specific role for JMJD3 in regulating the expression of genes that allow MuSCs to adapt to the modified niche of regenerating muscle. We aim to determine the differential occupancy of histone H3 lysine 4 trimethyl mark muscle satellite stem cells isolated from JMJD3scKO, UTXscKO and Wild-type mice.
2022-08-04 | GSE186829 | GEO
Project description:Stem cells reside in specialized niches that play a critical role in modulating their fate. Supporting cells in the niche instruct fate changes to the stem cells through epigenetic enzymes that transduce cell signaling to modify gene expression. Recent studies showed that the innate immune response to muscle injury alters the muscle stem cell (MuSC) niche, it remains unknown how MuSC adapt to the modified milieu to mediate muscle repair. Here we show that the epigenetic enzyme JMJD3 coordinates MuSC adaptation to the regenerative niche in a non-cell autonomous manner where it modifies their extracellular matrix to integrate signaling that stimulates exit of quiescence. Genomics and transcriptomics approaches identified the hyaluronic acid (HA) synthesis enzyme Has2 as a key JMJD3 target gene that allows MuSCs to integrate signals from the regenerative niche. Overall, we identified a specific role for JMJD3 in regulating the expression of genes that allow MuSCs to adapt to the modified niche of regenerating muscle. We aim to determine the differential occupancy of histone H3 lysine 4 trimethyl mark muscle satellite stem cells isolated from JMJD3scKO, UTXscKO and Wild-type mice.
2022-08-04 | GSE186828 | GEO
Project description:During aging, the regenerative capacity of skeletal muscle decreases due to intrinsic changes in muscle stem cells (MuSCs) and alterations in their niche. Here, we used quantitative mass spectrometry to characterize intrinsic changes in the MuSC proteome and remodeling of the MuSC niche during aging. We generated a network connecting age-affected ligands located in the niche and cell surface receptors on MuSCs. Thereby, we revealed signaling via Integrins, Lrp1, Egfr and Cd44 as the major cell communication axes perturbed through aging. We investigated the effect of Smoc2, a secreted protein that accumulates with aging, originating from fibro-adipogenic progenitors. Increased levels of Smoc2 contribute to the aberrant Itgb1/MAPK signaling observed during aging, thereby causing impaired MuSC functionality and muscle regeneration. By connecting changes in the proteome of MuSCs to alterations of their niche, our work will enable a better understanding of how MuSCs are affected during aging.
2021-11-10 | PXD023643 | Pride
Project description:During aging, the regenerative capacity of skeletal muscle decreases due to intrinsic changes in muscle stem cells (MuSCs) and alterations in their niche. Here, we used quantitative mass spectrometry to characterize intrinsic changes in the MuSC proteome and remodeling of the MuSC niche during aging. We generated a network connecting age-affected ligands located in the niche and cell surface receptors on MuSCs. Thereby, we revealed signaling via Integrins, Lrp1, Egfr and Cd44 as the major cell communication axes perturbed through aging. We investigated the effect of Smoc2, a secreted protein that accumulates with aging, originating from fibro-adipogenic progenitors. Increased levels of Smoc2 contribute to the aberrant Itgb1/MAPK signaling observed during aging, thereby causing impaired MuSC functionality and muscle regeneration. By connecting changes in the proteome of MuSCs to alterations of their niche, our work will enable a better understanding of how MuSCs are affected during aging.
2021-11-10 | PXD023628 | Pride
Project description:Muscle stem cells (MuSC) exhibit distinct behaviors during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated is poorly understood. Here we show that fetal MuSC resist progenitor specification and exhibit altered division dynamics, intrinsic features that are progressively lost postnatally. Following transplantation, fetal MuSC more efficiently expand and contribute to muscle repair. Conversely, the efficiency of niche colonization increases in adulthood, indicating a balance between muscle growth and stem cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM) molecules preferentially expressed in fetal MuSC, including tenascin-C, fibronectin and collagen VI. Loss-of-function experiments confirmed their essential and stage-specific role in regulating MuSC function. Finally, fetal-derived paracrine factors were able to enhance adult MuSC regenerative potential. Together, these findings demonstrate that MuSC change the way in which they remodel their microenvironment to direct stem cell behavior in support of the unique demands of muscle development or repair. MuSCs were isolated through fluorescent-activate cell sorting usinf alpha7-integirn and CD34 as markers to identify the cell population. Total mRNA was then isolated, and samples at different developmental times were compared.
2016-01-20 | E-GEOD-76989 | biostudies-arrayexpress
Project description:Adhesion between stem cells and their niche promotes stable niche localization and provides signaling information to sustain properties such as quiescence. Skeletal muscle stem cells (MuSCs) are localized between an adjacent myofiber and an enwrapping basal lamina. The most abundant cadherin in MuSCs, M-cadherin, is dispensable for MuSC function, whereas N-cadherin is required to prevent MuSCs from breaking quiescence in the absence of injury. Loss of both cadherins exacerbates this phenotype, yet the MuSCs remain in the niche and maintain regenerative function. These findings raise the possibility that cadherins are dispensable for anchorage of MuSCs to their niche. To address this question, we conditionally removed from MuSCs b- and g-catenin and, separately, aE- and aT-catenin, factors essential for cadherin-dependent adhesion. Catenin-deficient MuSCs break quiescence similarly to N-/M-cadherin-deficient MuSCs, but exit the niche, and are depleted via a single fate: precocious differentiation, reentry to the niche, and fusion to myofibers. These findings indicate that separable, cadherin-dependent functions are required in MuSCs for niche localization, quiescence, and stem cell maintenance.
2024-03-07 | GSE244181 | GEO
Project description:Background: Skeletal muscle crucially depends on motor innervation, and, when damaged, on the resident muscle stem cells (MuSCs). However, the role and function of MuSCs in the context of denervation remains poorly understood. Methods: Alterations of MuSCs and their myofiber niche after denervation were investigated in a surgery-based mouse model of unilateral sciatic nerve transection. FACS-isolated MuSCs were subjected to RNA-sequencing and mass spectrometry for the analysis of intrinsic changes after denervation and in vivo assays, such as Cardiotoxin-induced muscle injury or MuSC transplantation, were performed to assess MuSC functions after denervation. Bioinformatic and histological analyses were conducted to further examine MuSCs and their myofiber niche after denervation. Results: Muscle cross section analysis revealed a significant increase in Pax7 (p-value= 0.0441), Pax7/Ki67 (p-value= 0.0023), MyoD (p-value= 0.0016) and Myog (p-value= 0.0057) positive cells after denervation, illustrating a break of quiescence and commitment to the myogenic lineage. An Omics approach showed profound intrinsic alterations on the mRNA (2613 differentially expressed genes, p-value <0.05) and protein (1096 differentially abundant proteins, q-value <0.05) level of MuSCs 21 days after denervation. Skeletal muscle injury together with denervation surgery caused deregulated regeneration, indicated by the reduced number of proliferating MuSCs and sustained high levels of developmental myosin heavy chain (Sham: 1 % vs DEN: 40 % of all myofibers), at 21 days post-surgery. In a transplantation assay, MuSCs from a denervated host were still able to engraft and fuse to form new myofibers, irrespective of the innervation status of the recipient muscle. Analysis of myofibers revealed not only massive changes in the expression profile (10492 differentially expressed genes, p-value <0.05) after denervation, but it was also shown that secretion of Opn and Tgfb1 from denervated myofibers was increased 30-fold and 6000-fold, respectively. Bioinformatic analyses indicated strong upregulation of gene expression of the transcription factor Junb in MuSCs from denervated muscles (log2 fold change = 3.27). Of interest, Tgfb1 recombinant protein was able to induce Junb gene expression in vitro, demonstrating that myofiber-secreted ligands can induce gene expression changes in MuSCs, which might result in the phenotypes observed after denervation. Conclusion: Skeletal muscle denervation is altering myofiber secretion, causing MuSC activation and profound intrinsic changes, leading to reduced regenerative capacity. As MuSCs possess a remarkable regenerative potential, they might represent a promising target for novel treatment options for neuromuscular disorders and peripheral nerve injuries.
2024-02-27 | PXD036993 | Pride
Project description:Background: Skeletal muscle function crucially depends on motor innervation and after injury on the resident muscle stem cells (MuSCs). However, it is poorly understood how innervation affects MuSC properties. Methods: We investigated the alterations of MuSCs and their immediate niche, the myofiber, after denervation in a surgery-based mouse model of unilateral sciatic nerve transection. FACS-isolated MuSCs were subjected to transcriptomics and proteomics analyses to investigate which changes occur after denervation. We performed Cardiotoxin-induced muscle injury, MuSC transplantation and floating myofiber cultures to assess MuSC functionality after denervation in addition to bioinformatics and histological analyses. Results: We observed a significant increase in the number of MuSCs (Pax7 positive; p-value= 0.0441), proliferating MuSCs (Pax7/Ki67 positive; p-value= 0.0023), activated MuSCs (MyoD positive; p-value= 0.0016) and differentiating MuSCs (Myog positive; p-value= 0.0057) after denervation. This aberrant activation and premature commitment of MuSCs to the myogenic lineage was accompanied by profound alterations on the mRNA (2613 differentially expressed genes, adj. p-value <0.05) and protein (1096 differentially abundant proteins, q-value <0.05) level after denervation. MuSCs from denervated hosts still engrafted and fused to form new myofibers irrespective of the innervation status of the recipient, suggesting the MuSC niche is driving alterations in MuSCs after denervation. The myofiber transcriptome after denervation showed massive changes in the general expression profile (10492 DEGs, p-value <0.05) and in several predicted secreted factors. Incubation of myofiber-associated MuSCs with supernatant from denervated myofibers increased cluster formation, reinforcing myofibers as a source of secreted factors driving MuSC alterations after denervation. Opn and Tgfb1 showed an increased secretion by denervated myofibers (30-fold and 6000-fold, respectively), and incubation with Tgfb1 alone induced Junb expression in myogenic cells, one of the genes highly upregulated in MuSCs after denervation (p-value= 1.85e-18, log2fc= 3.27), demonstrating that myofiber-secreted ligands influence MuSC gene expression. A combination of skeletal muscle injury and denervation led to reduced numbers of proliferating MuSCs (Sham: 47 vs DEN: 19.75 cells per cross section 10 days post-injury) and sustained high levels of developmental myosin heavy chain (Sham: 1 % vs DEN: 40 % of all myofibers 21 days post-injury), indicating hampered MuSC functionality due to changes in the microenvironment. Conclusion: Denervation of skeletal muscle causes alterations in myofiber secretion, leading to activation and profound changes of MuSCs, ultimately resulting in a reduced regenerative capacity. As these alterations are partially reversible, MuSCs are a promising target for novel treatment options for neuromuscular disorders and peripheral nerve injuries.
2024-03-04 | GSE217929 | GEO