Gli1 marks a sentinel muscle stem cell population for muscle regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1001793 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25501390_1.fastq.gz | Fastqsanger.gz | |||
| SRR25501390_2.fastq.gz | Fastqsanger.gz | |||
| SRR25501391_1.fastq.gz | Fastqsanger.gz | |||
| SRR25501391_2.fastq.gz | Fastqsanger.gz | |||
| SRR25501392_1.fastq.gz | Fastqsanger.gz |
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Project description:Adult skeletal muscle regeneration is mainly driven by muscle stem cells (MuSCs), which are highly heterogeneous. Although recent studies have started to characterize the heterogeneity of MuSCs, whether a subset of cells with distinct exists within MuSCs remains unanswered. Here, we found that a population of MuSCs, marked by Gli1 expression, is required for muscle regeneration. The Gli1+ MuSC population displayed advantages in proliferation and differentiation both in vitro and in vivo. Depletion of this population led to delayed muscle regeneration, while transplanted Gli1+ MuSCs supported muscle regeneration more effectively than Gli1- MuSCs. Further analysis revealed that even in the uninjured muscle, Gli1+ MuSCs had elevated mTOR signaling activity, increased cell size and mitochondrial numbers compared to Gli1- MuSCs, indicating Gli1+ MuSCs are displaying the features of primed MuSCs. Moreover, Gli1+ MuSCs greatly contributed to the formation of GAlert cells after muscle injury. Collectively, our findings demonstrate that Gli1+ MuSCs represent a distinct MuSC population which is more active in the homeostatic muscle and enters the cell cycle shortly after injury. This cell population functions as the tissue-resident sentinel that rapidly responds to injury and initiates muscle regeneration.
2023-08-06 | GSE239944 | GEO
Project description:Adult skeletal muscle regeneration is mainly driven by muscle stem cells (MuSCs), which are highly heterogeneous. Although recent studies have started to characterize the heterogeneity of MuSCs, whether a subset of cells with distinct exists within MuSCs remains unanswered. Here, we find that a population of MuSCs, marked by Gli1 expression, is required for muscle regeneration. The Gli1+ MuSC population displays advantages in proliferation and differentiation both in vitro and in vivo. Depletion of this population leads to delayed muscle regeneration, while transplanted Gli1+ MuSCs support muscle regeneration more effectively than Gli1- MuSCs. Further analysis reveals that even in the uninjured muscle, Gli1+ MuSCs have elevated mTOR signaling activity, increased cell size and mitochondrial numbers compared to Gli1- MuSCs, indicating Gli1+ MuSCs are displaying the features of primed MuSCs. Moreover, Gli1+ MuSCs greatly contribute to the formation of GAlert cells after muscle injury. Collectively, our findings demonstrate that Gli1+ MuSCs represents a distinct MuSC population which is more active in the homeostatic muscle and enters the cell cycle shortly after injury. This population functions as the tissue-resident sentinel that rapidly responds to injury and initiates muscle regeneration.
| S-EPMC10620419 | biostudies-literature
Project description:In the vertebrate neural tube, regional Sonic hedgehog (Shh) signaling invokes a time- and concentration-dependent induction of six different cell populations mediated through Gli transcriptional regulators. Elsewhere in the embryo, Shh/Gli responses invoke different tissue appropriate regulatory programs. To elucidate Shh/Gli regulation of neural fate sepcification, we performed Gli1 ChIP-Seq analysis. We further analyzed two transcription factors whose motifs were enriched in Gli1 ChIP data (Sox2 and Foxa2). Two active histone marks (H3K4me2 and H3K27ac) were additionally analyzed to study activity status of Shh-responsive cis-elements. Active enhancer histone marks and transcription factor binding patterns were obtained from neuralized emrbyoid bodies. Biological replicates were performed for Gli1 and mock FLAG chips. Histone profiling for enhancer marks were taken from time course experiment performed in parallel.
2012-12-15 | E-GEOD-42132 | biostudies-arrayexpress
Project description:In the vertebrate neural tube, regional Sonic hedgehog (Shh) signaling invokes a time- and concentration-dependent induction of six different cell populations mediated through Gli transcriptional regulators. Elsewhere in the embryo, Shh/Gli responses invoke different tissue appropriate regulatory programs. To elucidate Shh/Gli regulation of neural fate sepcification, we performed Gli1 ChIP-Seq analysis. We further analyzed two transcription factors whose motifs were enriched in Gli1 ChIP data (Sox2 and Foxa2). Two active histone marks (H3K4me2 and H3K27ac) were additionally analyzed to study activity status of Shh-responsive cis-elements.
2012-12-15 | GSE42132 | GEO
Project description:Repair-supportive mesenchymal cells (RSMCs) have been recently reported in the context of naphthalene (NA)-induced airway injury and regeneration. These cells transiently express smooth muscle actin (Acta2) and are enriched with platelet-derived growth factor receptor alpha (Pdgfra) and fibroblast growth factor 10 (Fgf10) expression. Genetic deletion of Ctnnb1 (gene coding for beta catenin) or Fgf10 in these cells using the Acta2-Cre-ERT2 driver line after injury (defined as NA-Tam condition; Tam refers to tamoxifen) led to impaired repair of the airway epithelium. In this study, we demonstrate that RSMCs are mostly captured using the Acta2-Cre-ERT2 driver when labeling occurs after (NA-Tam condition) rather than before injury (Tam-NA condition), and that their expansion occurs mostly between days 3 and 7 following NA treatment. Previous studies have shown that lineage-traced peribronchial GLI1+ cells are transiently amplified after NA injury. Here, we report that Gli1 expression is enriched in RSMCs. Using lineage tracing with Gli1Cre-ERT2 mice combined with genetic inactivation of Fgf10, we show that GLI1+ cells with Fgf10 deletion fail to amplify around the injured airways, thus resulting in impaired airway epithelial repair. Interestingly, Fgf10 expression is not upregulated in GLI1+ cells following NA treatment, suggesting that epithelial repair is mostly due to the increased number of Fgf10-expressing GLI1+ cells. Co-culture of SCGB1A1+ cells with GLI1+ cells isolated from non-injured or injured lungs showed that GLI1+ cells from these two conditions are similarly capable of supporting bronchiolar organoid (or bronchiolosphere) formation. Single-cell RNA sequencing on sorted lineage-labeled cells showed that the RSMC signature resembles that of alveolar fibroblasts. Altogether, our study provides strong evidence for the involvement of mesenchymal progenitors in airway epithelial regeneration and highlights the critical role played by Fgf10-expressing GLI1+ cells in this context.
2022-11-09 | GSE215094 | GEO
Project description:We sought to determine the effects of over-expression of Gli1 on gene expression in C2C12 myotube cultures. C2C12 myoblasts were induced to differentiate for 4 days. At that time, when >80% of nuclei were incorporated into multi-nucleated syncitial myotubes, we infected the cultures with recombinant adenovirus expressing GFP alone or GFP and a full length human Gli1. Media was changed 12 hours later. Cultures were lysed 60 hours after the initial infection. Gli1 over-expression induces de-differentiation of myotubes and proliferation of myoblasts. Results provide insight into the molecular basis of SHH signaling on skeletal muscle cells.
2013-12-01 | E-GEOD-37702 | biostudies-arrayexpress
Project description:GLI1 is a transcription factor correlated to decreased survival in several cancers. We have identified SMARCA2 as a co-regulator that enhances GLI1-mediated transcriptional activity and functions through the C-terminal transcriptional activation domain of GLI1. Central domains including the ATPase motif of SMARCA2 physically interact with GLI1. Evaluation of DNA density indicates GLI1, like SMARCA2, can increase the DNA accessibility with a preference for sites distal to gene transcription start sites and outside the promoter regions (i.e. enhancers). The putative enhancers where accessibility is decreased by the knock down of GLI1 and SMARCA2 are located cis to genes, such as HHIP, that are regulated by GLI1 and implicated in cancer functions. At the putative enhancer for HHIP, the localization of SMARCA2 is at least partially dependent on GLI1’s presence. Understanding this transcriptional regulation by GLI1 and SMARCA2 through altering chromatin accessibility at enhances can provide additional therapeutic targets for cancers dependent on GLI1.
2020-05-11 | GSE143684 | GEO
Project description:Increased expression of GLI1 is associated with poor prognosis for some breast cancer subtypes. A conditional transgenic GLI1 expressing mouse model, with or without heterozygous deletion of Trp53, was used to generate and study GLI1 induced mammary gland tumours. Tumour tissue was serially orthotopically transplanted for at least 10 generations in NSG mice.
2019-06-30 | E-MTAB-7531 | biostudies-arrayexpress
Project description:The precise origin of newly formed alpha smooth muscle actin-positive (ACTA2+) cells appearing in non-muscularized vessels in the context of pulmonary hypertension (PH) is still debatable, although it is believed that they predominantly derive from pre-existing vascular smooth muscle cells (VSMCs). Here, Gli1Cre-ERT2; tdTomatoflox mice were used to lineage-trace GLI1+ cells in the context of PH using two independent models of vascular remodeling (VR) and reverse remodeling (RR): Hypoxia and cigarette-smoke exposure (SE). Hemodynamic measurements, right ventricular hypertrophy assessment, flow cytometry, and histological analysis of thick lung sections followed by state-of-the-art 3D reconstruction and quantification using Imaris software were used to investigate the contribution of GLI1+ cells to neo-muscularization of the pulmonary vasculature. The data show that GLI1+ cells are abundant around distal, nonmuscularized vessels during steady state, and that this lineage contributes to around 50% of newly formed ACTA2+ cell around these normally non-muscularized vessels. During RR, cells derived from the GLI1+ lineage are largely cleared in parallel to the reversal of muscularization. Partial ablation of GLI1+ cells greatly prevented VR in response to hypoxia and attenuated the increase in RVSP and right heart hypertrophy. Single-cell RNA sequencing (scRNA-seq) on sorted lineage-labeled GLI1+ cells revealed an Acta2high fraction of cells with pathways in cancer and MAPK signaling as potential players in reprogramming these cells during VR. Analysis of human lungderived material suggests that GLI1 signaling is overactivated in both Group 1 and Group 3 PH and can promote proliferation and myogenic differentiation. Our data highlight GLI1+ cells as an alternative cellular source of VSMCs in PH and suggest that these cells and the associated signaling pathways represent an important therapeutic target for further studies.
2024-05-14 | GSE253415 | GEO