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Fibronectin regulates Wnt7a signaling and satellite cell expansion

ABSTRACT: The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE59272 | GEO | 2014/07/11

SECONDARY ACCESSION(S): PRJNA255003

REPOSITORIES: GEO

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Fibronectin regulates Wnt7a signaling and satellite cell expansion

Project description:The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis. The data set contains one microarray of pooled quiescent skeletal muscle satellite cells

2014-07-11 | E-GEOD-59272 | biostudies-arrayexpress

Sex hormones establish a reserve pool of adult muscle stem cells at puberty

Project description:Quiescent satellite cells, also known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle upon injury throughout life. Although they mainly originate from multipotent stem/progenitors of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb-1 (Mib1) expression in myofibers at puberty, which activates Notch signaling in cycling juvenile satellite cells and causes them to be converted into quiescent adult satellite cells. Myofibers lacking Mib1 failed to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Genetic and inhibitor studies revealed that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofiber niche. Our data show how sex hormones establish quiescent adult satellite cell populations by regulating the myofiber niche at puberty. Microarray analysis of Veh or DHT-injected 10-day-old mice s.c. injected with Veh or DHT. TA muscles were isolated 24 h after the injection.

2015-09-01 | E-GEOD-64454 | biostudies-arrayexpress

DECREASED FIBRONECTIN PRODUCTION SIGNIFICANTLY CONTRIBUTES TO DYSREGULATED REPAIR OF ASTHMATIC EPITHELIUM

Project description:Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from asthmatic children fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n=36), healthy atopic (n=23) and healthy non-atopic controls (n=53) were investigated by microarray, gene expression and silencing, transcript regulation analysis and ability to close mechanical wounds. Results: Wound repair of AEC from healthy and atopic children were not significantly different and were both faster than AEC from asthmatics. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by qPCR and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in non-asthmatic AEC inhibited wound repair, while addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5â, 2âdeoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells. 16 arrays, 2 experimental groups, asthma atopic, AA, and healthy non-atopic, HN.

2010-04-12 | E-GEOD-18965 | biostudies-arrayexpress

Transcriptome analysis of genetically engineered murine fusion-negative rhabdomyosarcoma model-derived cell lines

Project description:Fusion-negative rhabdomyosarcoma (FN-RMS) is the most common soft tissue sarcoma of childhood arising from undifferentiated skeletal muscle cells. Tumor cells derived from genetically engineered murine models are a valid tool to study cancer biology. In order to investigate the poor myogenic commitment of FN-RMS, we performed RNA sequencing of two cell lines derived from a previously described genetically engineered murine model of FN-RMS. We then performed bioinformatics analysis to compare the transcriptome with murine satellite cells, and identify the key factors that distinguish FN-RMS from skeletal muscle cells.

2021-05-31 | GSE175816 | GEO

Quantification of local matrix deposition during muscle stem cell activation using engineered hydrogels

Project description:Adult stem cells occupy a niche that contributes to their function but how stem cells remodel their microenvironment remains an open-ended question. Herein, biomaterials-based systems and metabolic labeling were utilized to evaluate how skeletal muscle stem cells and mesenchymal progenitors (fibro-adipogenic progenitors) deposit and remodel extracellular matrix. Differences in matrix production of muscle stem cells on substrates with different stiffness were then evaluated and linked with stem cell activation state. Reducing the ability to deposit new matrix attenuated function and mimicked impairments observed from muscle stem cells isolated in old age. Rescuing nascent protein deposition in old age stem cells with therapeutic supplementation rescued extracellular protein deposition and highlight how important this feature of niche remodeling is towards maintaining healthy stem cell function.

2024-02-15 | GSE252829 | GEO

DECREASED FIBRONECTIN PRODUCTION SIGNIFICANTLY CONTRIBUTES TO DYSREGULATED REPAIR OF ASTHMATIC EPITHELIUM

Project description:Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from asthmatic children fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n=36), healthy atopic (n=23) and healthy non-atopic controls (n=53) were investigated by microarray, gene expression and silencing, transcript regulation analysis and ability to close mechanical wounds. Results: Wound repair of AEC from healthy and atopic children were not significantly different and were both faster than AEC from asthmatics. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by qPCR and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in non-asthmatic AEC inhibited wound repair, while addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5’, 2’deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells.

2010-03-31 | GSE18965 | GEO

Stem cell niche organisation in the Drosophila ovary requires the ECM component Perlecan

Project description:Stem cells reside in specialised microenvironments or niches that balance stem cell proliferation and differentiation. The extracellular matrix (ECM) is an essential component of most niches, as it controls niche homeostasis, provides physical support and conveys extracellular signals. Basement membranes (BMs) are thin ECM sheets constituted mainly by Laminins, Perlecan, Collagen IV and Entactin/Nidogen and that surround epithelia and other tissues. Perlecans are secreted proteoglycans that interact with ECM proteins, ligands, receptors and growth factors such as FGF, PDGF, VEGF, Hedgehog and Wingless. Thus, Perlecans have structural and signalling functions through the binding, storage or sequestering of specific ligands. We have used the Drosophila ovary to assess the importance of Perlecan in the functioning of a stem cell niche. Ovarioles in the adult ovary are enveloped by an ECM sheath and possess a tapered structure at their anterior apex termed the germarium. The anterior tip of the germarium hosts the germline niche, where two to four germline stem cells (GSCs) reside together with few somatic cells: terminal filament (TF) cells, cap cells (CpCs) and escort cells (ECs). We report that niche architecture in the developing gonad requires trol, that niche cells secrete an isoform-specific, Perlecan-rich interstitial matrix and that DE-cadherin-dependent stem cell-niche adhesion necessitates trol. Hence, we provide evidence to support a structural role for Perlecan in germline niche establishment during larval stages and in the maintenance of a normal pool of stem cells in the adult niche.

2021-03-31 | GSE164866 | GEO

Sex hormones establish a reserve pool of adult muscle stem cells at puberty

2015-09-01 | GSE64454 | GEO

Autonomous extracellular matrix remodeling controls a progressive adaptation in muscle stem cell regenerative capacity during development

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