Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA170741 | ENA |
REPOSITORIES: ENA
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Project description:Skeletal muscle growth and regeneration rely on myogenic progenitor and satellite cells, the stem cells of postnatal muscle. Elimination of Notch signals during mouse development results in premature differentiation of myogenic progenitors and formation of very small muscle groups. Here we show that this drastic effect is rescued by mutation of the muscle differentiation factor MyoD. However, rescued myogenic progenitors do not assume a satellite cell position and contribute poorly to myofiber growth. The disrupted homing is due to a deficit in basal lamina assembly around emerging satellite cells and to their impaired adhesion to myofibers. On a molecular level, emerging satellite deregulate the expression of basal lamina components and adhesion molecules like integrin a7, collagen XVIIIa1, Megf10 and Mcam. We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers. Gene expression analysis using total RNA from FACS-isolated Vcam-1+/CD31-/CD45-/Sca1- embryonic muscle progenitor cells from E17.5 back muscle tissue of MyoD-/-, Pax3cre/+;Rbpjflox/flox;MyoD-/- and Pax3cre/+;DnMamlflox/flox;MyoD-/- mice.
2012-12-31 | E-GEOD-39379 | biostudies-arrayexpress
Project description:Fibro adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fatty infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin- deficient mdx mice are insensitive to this control mechanism. An unbiased mass spectrometry-based proteomic analysis of FAPs from muscles of wild type and mdx mice, suggest that the synergistic cooperation between NOTCH and inflammatory signals controls FAP differentiation. Remarkably, we demonstrated that factors released by hematopoietic cells restore the sensitivity to NOTCH adipogenic inhibition in mdx FAPs. These results offer a basis for rationalizing pathological ectopic fat infiltrations in skeletal muscle and may suggest new therapeutic strategies to mitigate the detrimental effects of fat depositions in muscles of dystrophic patients.
2019-06-24 | PXD014195 | Pride
Project description:During developmental myogenesis, some continuously proliferating myogenic progenitors (MPs) sustain stem/progenitor states while the rest differentiate into myocytes to form myofibers by fusion. To generate sufficient muscle, fine regulations of cell fate decision of MPs are crucial. Notch signaling has been known to regulate embryonic MPs (eMPs) that play a role in primary myogenesis by promoting cell cycle exit and suppressing premature differentiation. However, the role of Notch signaling in fetal MPs (fMPs) during secondary myogenesis is elusive because the development of fMPs already has been abrogated in Notch manipulation models. In this study, we investigated the role of Notch signaling in fMPs at an individual Notch receptor level. Surprisingly we found that Notch1 and Notch2, most similar among four Notch receptors, distinctly regulate fMPs: Notch1 induces cell cycle exit and Notch2 suppresses premature differentiation, presumably by canonical Notch signaling pathway. Additionally, we suggest that Notch1 and Notch2 signals are regulated by the ligands on myofibers and MP-lineage cells, respectively. This study will lay the groundwork for the in-depth understanding of Notch signaling in muscle formation from embryonic myogenesis to adult muscle regeneration.
2022-12-31 | GSE190521 | GEO
Project description:Skeletal muscle growth and regeneration rely on myogenic progenitor and satellite cells, the stem cells of postnatal muscle. Elimination of Notch signals during mouse development results in premature differentiation of myogenic progenitors and formation of very small muscle groups. Here we show that this drastic effect is rescued by mutation of the muscle differentiation factor MyoD. However, rescued myogenic progenitors do not assume a satellite cell position and contribute poorly to myofiber growth. The disrupted homing is due to a deficit in basal lamina assembly around emerging satellite cells and to their impaired adhesion to myofibers. On a molecular level, emerging satellite deregulate the expression of basal lamina components and adhesion molecules like integrin a7, collagen XVIIIa1, Megf10 and Mcam. We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers.
2012-12-31 | GSE39379 | GEO
Project description:It has been shown recently that non-coding RNAs including miRNAs are involved in the development of skeletal muscle progenitors and to maintain the quiescent condition of adult skeletal muscle stem cells. To identify the difference among developing skeletal muscle-committed progenitors or stem cells detected by Pax3-GFP; MyoD-primed RFP expressions, miRNA microarray was performed. Pax3-GFP; MyoD-RFP positive cells were selected at several developmental stages for miRNA extraction and hybridization on Affymetrix
2014-08-01 | E-GEOD-48412 | biostudies-arrayexpress
Project description:The canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor represses differentiation. We now identify Barx2,MyoD,and Pax7 as novel components of the Wnt effector complex, providing a new molecular pathway for regulation of muscle progenitor differentiation. Canonical Wnt signaling induces Barx2 expression in muscle progenitors and perturbation of Barx2 leads to misregulation of Wnt target genes. Barx2 activates two endogenous Wnt target promoters as well as the Wnt reporter gene TOPflash, the latter synergistically with MyoD. Moreover, Barx2 interacts with the core Wnt effectors β-catenin and TCF, is recruited to TCF/LEF sites, and promotes recruitment of β-catenin. In contrast, Pax7 represses the Wnt reporter gene and antagonizes the activating effect of Barx2. Pax7 also binds β-catenin suggesting that Barx2 and Pax7 may compete for interaction with the core Wnt effector complex. Overall, the data show for the first time that Barx2, Pax7, and MRFs can act as direct transcriptional effectors of Wnt signals in myoblasts and that Barx2 and Wnt signaling participate in a regulatory loop. We propose that antagonism between Barx2 and Pax7 in regulation of Wnt signaling may help mediate the switch from myoblast proliferation to differentiation. RNA-Seq analyses was used to characterize gene expression in primary myoblasts from wild-type and Barx2 knockout mice.
2015-10-22 | E-GEOD-53398 | biostudies-arrayexpress
Project description:Coordination of signaling pathways is essential for tissue homeostasis and for preventing cancer development. Here, we show that the E3 ligase Rnf8, an important component of the DNA double-strand break (DSB) signaling, is critical for cell-fate commitment of the mammary epithelial progenitors. Furthermore, we provide evidence that deficiency of Rnf8 predisposes mouse models for mammary tumorigenesis while low expression levels in breast cancer associates with poor patient prognosis. RNF8 mediates these novel functions through ubiquitylation and degradation of the activated form of NOTCH1, and thereby fine-tuning of NOTCH signaling. Accordingly, RNF8 level negatively correlates with the expression of NOTCH targets in mouse mammary and human breast tumors. Consistent with these findings, Rnf8-deficient mammary tumors are highly sensitive to pharmacological inhibition of NOTCH. Therefore, RNF8 inhibits breast cancer on two fronts, maintaining genomic stability through DSB signaling and regulating growth and differentiation through inhibition of the NOTCH pathway.
2017-01-01 | GSE76075 | GEO
Project description:The canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor represses differentiation. We now identify Barx2,MyoD,and Pax7 as novel components of the Wnt effector complex, providing a new molecular pathway for regulation of muscle progenitor differentiation. Canonical Wnt signaling induces Barx2 expression in muscle progenitors and perturbation of Barx2 leads to misregulation of Wnt target genes. Barx2 activates two endogenous Wnt target promoters as well as the Wnt reporter gene TOPflash, the latter synergistically with MyoD. Moreover, Barx2 interacts with the core Wnt effectors β-catenin and TCF, is recruited to TCF/LEF sites, and promotes recruitment of β-catenin. In contrast, Pax7 represses the Wnt reporter gene and antagonizes the activating effect of Barx2. Pax7 also binds β-catenin suggesting that Barx2 and Pax7 may compete for interaction with the core Wnt effector complex. Overall, the data show for the first time that Barx2, Pax7, and MRFs can act as direct transcriptional effectors of Wnt signals in myoblasts and that Barx2 and Wnt signaling participate in a regulatory loop. We propose that antagonism between Barx2 and Pax7 in regulation of Wnt signaling may help mediate the switch from myoblast proliferation to differentiation.
2015-10-22 | GSE53398 | GEO
Project description:It has been shown recently that non-coding RNAs including miRNAs are involved in the development of skeletal muscle progenitors and to maintain the quiescent condition of adult skeletal muscle stem cells. To identify the difference among developing skeletal muscle-committed progenitors or stem cells detected by Pax3-GFP; MyoD-primed RFP expressions, miRNA microarray was performed.
2014-08-01 | GSE48412 | GEO