PW1/Peg3 expression regulates the key properties that determine mesoangioblast stem cell competence
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64334 | GEO | 2015/01/19
SECONDARY ACCESSION(S): PRJNA270758
REPOSITORIES: GEO
Similar Datasets
Project description:Mesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/Peg3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/Peg3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/Peg3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibers through the modulation of the junctional adhesion molecule-A. We conclude that PW1/Peg3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/Peg3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies. Ctrl Mesoangioblasts (MABs) transduced with a Lentiviral vector shControl (2 replicates, Ctrl_1 and Ctrl_2) and shPW1 Mesoangioblasts transduced with a Lentiviral vector shPW1 (2 replicates, PW1-siRna_1 and PW1-siRna_2)
2015-01-19 | E-GEOD-64334 | biostudies-arrayexpress
Project description:Cardiac resident stem/progenitor cells are intensively studied as a potential therapeutic tool for cardiomyopathies. While surface marker expression and ability to generate cardiomyocytes have been characterized in some detail for several types of these progenitors, little is known on how their cardiac differentiation is regulated. Beta sarcoglycan null (bSG KO) mice are a model for limb girdle muscular dystrophy type 2E (LGMD2E), and are characterized by muscular dystrophy and progressive dilated cardiomyopathy. In the present study we isolated and characterized cardiac progenitors (mesoangioblasts) from the small vessels of neonatal hearts bSG KO mice and unexpectedly observed that they differentiate spontaneously into skeletal muscle fibers both in vitro and when transplanted in regenerating muscles and infarcted hearts. The micro array data showed that dystrophic cardiac progenitor and myogenic cells (C2C12) share similar gene expression profile. Keywords: Beta sarcoglycan null mice, muscular dystrophy, cardiac mesoangioblasts, myogenic differentiation Biological triplicates of cardiac wild-type and dystrophic mesoangioblasts isolated from different heart region (atrium, ventricle, aorta) were compared. C2C12 cells were used as positive control for myogenic differentiation.
2011-04-19 | E-GEOD-17774 | biostudies-arrayexpress
Project description:Cardiac resident stem/progenitor cells are intensively studied as a potential therapeutic tool for cardiomyopathies. While surface marker expression and ability to generate cardiomyocytes have been characterized in some detail for several types of these progenitors, little is known on how their cardiac differentiation is regulated. Beta sarcoglycan null (bSG KO) mice are a model for limb girdle muscular dystrophy type 2E (LGMD2E), and are characterized by muscular dystrophy and progressive dilated cardiomyopathy. In the present study we isolated and characterized cardiac progenitors (mesoangioblasts) from the small vessels of neonatal hearts bSG KO mice and unexpectedly observed that they differentiate spontaneously into skeletal muscle fibers both in vitro and when transplanted in regenerating muscles and infarcted hearts. The micro array data showed that dystrophic cardiac progenitor and myogenic cells (C2C12) share similar gene expression profile. Keywords: Beta sarcoglycan null mice, muscular dystrophy, cardiac mesoangioblasts, myogenic differentiation
2011-04-19 | GSE17774 | GEO
Project description:Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging. Given the paracrine properties of myogenic stem cells, extracellular vesicle-derived signals have been studied for their potential implication in both the pathogenesis of degenerative neuromuscular diseases and as a possible therapeutic target. In this study, we screened the content of extracellular vesicles from animal models of muscle hypertrophy and muscle wasting associated with chronic disease and aging. Analysis of the transcriptome, protein cargo and microRNAs (miRNAs) allowed us to identify a hypertrophic miRNA signature amenable for targeting muscle wasting, consisting of miR-1 and miR-208a. We tested this signature among others in vitro on mesoangioblasts (MABs), vessel-associated adult stem cells, and we observed an increase in the efficiency of myogenic differentiation. Furthermore, injections of miRNA-treated MABs in aged mice resulted in an improvement in skeletal muscle features, such as muscle weight, strength and cross-sectional area compared to controls. Overall, we provide evidence that the extracellular vesicle-derived miRNA signature we identified enhances the myogenic potential of myogenic stem cells.
2022-11-09 | PXD035446 | Pride
Project description:The BM-derived CD45+/Sca1+ cells are haematopoietic stem/progenitor cells that have the ability to circulate and migrate and engraft to the muscle tissue, and therefore they are of particular interest. Notably, these cells retain their haematopoietic potential, as revealed both by in vitro and in vivo assays; but they also acquire myogenic potential, as shown by their ability to participate in muscle regeneration. Whether, this latter remarkable ability is the result of the reprogramming of the BM-CD45+/Sca1+ cells and the activation of a myogenic molecular program within these cells, remains controversial. This study aims to clarify this aspect of the process, investigating the role of the muscle microenviroment and key myogenic transcription factors. Keywords: CD45+/Sca1+ cells, BM, muscle CD45+/Sca1+ cells isolated from the BM or the muscle were processed fresh and their RNA was extracted. Moreover, CD45+/Sca1+ cells isolated from the muscle of BM transplanted or untransplanted mice after injury with Cardiotoxin were processed fresh and their RNA was extracted.
2010-04-05 | E-GEOD-9296 | biostudies-arrayexpress
Project description:Mesodermal iPSC derived progenitors (MiPs) obtained from human fetal fibroblasts and skeletal muscle mesoangioblasts show a different myogenic potential in vitro and when injected in vivo in mice model of Muscular Dystrophy. MAB-MiPs hold greater myogenic commitment compared to f-MiPs, showed by increased engraftment and regeneration of the hindlimb muscle. Here we report that RNA sequencing of MiPs and of induced pluripotent stem cells (iPSCs) of origin allows identification of genes differentially regulated between fibroblast and MABs progenies that might be responsible for the different contribution to muscle regeneration. MicroRNA- sequencing of the same cell lines further allowed a selection of a set of miRNAs that can drive the myogenic propensity of MiPs in vivo and identification of promyogenic and antimyogenic miRNA cocktails. Manipulation of the selected miRNAs improved the engraftment and regeneration of MiPs. Additional RNA-sequencing after the treatment with the defined promyogenic and antimyogenic cocktails unraveled additional information on the pathways modulated by the selected factors.
2017-09-14 | GSE102283 | GEO
Project description:The BM-derived CD45+/Sca1+ cells are haematopoietic stem/progenitor cells that have the ability to circulate and migrate and engraft to the muscle tissue, and therefore they are of particular interest. Notably, these cells retain their haematopoietic potential, as revealed both by in vitro and in vivo assays; but they also acquire myogenic potential, as shown by their ability to participate in muscle regeneration. Whether, this latter remarkable ability is the result of the reprogramming of the BM-CD45+/Sca1+ cells and the activation of a myogenic molecular program within these cells, remains controversial. This study aims to clarify this aspect of the process, investigating the role of the muscle microenviroment and key myogenic transcription factors. Keywords: CD45+/Sca1+ cells, BM, muscle
2010-04-06 | GSE9296 | GEO
Project description:Mesoangioblasts are stem/progenitor cells derived from a subset of pericytes expressing alkaline phosphatase. They have been shown to ameliorate muscular dystrophies (currently incurable diseases) in different animal models and are now undergoing clinical experimentation for Duchenne muscular dystrophy. We show here that patients affected by limb-girdle muscular dystrophy 2D (LGMD2D, characterized by M-NM-1-sarcoglycan deficit) have a reduction of this subset of pericytes and hence mesoangioblast could not be derived for cell therapy. Therefore, we reprogrammed LGMD2D fibroblasts and myoblasts to induced pluripotent stem cells (iPSCs) and developed a protocol for the derivation of mesoangioblast-like cells from them. These cells can be expanded and genetically corrected with a muscle-specific lentiviral vector expressing human M-NM-1-sarcoglycan. Upon transplantation into ad hoc generated M-NM-1-sarcoglycan-null immunodeficient mice, they generate myofibers expressing M-NM-1-sarcoglycan. This approach may be useful for muscular dystrophies that show a reduction of resident progenitors and provides evidence of pre-clinical safety and efficacy of disease-specific iPSCs. 9 samples analyzed: 3 WT HIDEMs, 3 Limb-girdle muscular dystrophy 2D (LGMD2D) HIDEMs and 3 WT adult skeletal muscle derived mesoangioblasts (controls).
2012-07-08 | E-GEOD-36098 | biostudies-arrayexpress
Project description:While blood vessels have muscular walls that undergo tonic contractions to alter vascular resistance and, thus, control blood flow, lymphatics at the level of the collecting vessels and higher have muscular walls capable of rapid phasic contractions that generate lymph flow in addition to tonic contractions that regulate lymph flow resistance. While the ability of lymphatics to undergo rapid phasic contractions has been known for several centuries, the biological elements governing this phenomenon remain unknown. In an attempt to gain insight into the structural and regulatory elements that give lymphatic vessels their unique contractile capabilities, we utilized two-color microarray analysis to compare the thoracic duct of the rat to the vena cava of the same donor animal. Total cellular RNA was isolated immediately following vessel isolation and amplified in the presence of amino allyl dUTP. The resulting modified aRNA was conjugated to either Cy3 or Cy5 dye prior to hybridization to a rat 5.7K oligonucleotide array. Analysis and filtering of the data obtained from the microarray image yielded several contractile and regulatory genes with altered expression in the thoracic duct relative to the vena cava. Further evaluation of the data obtained in this study may aid in illustrating the unique properties of the lymphatic vessel and its muscular wall. Keywords: Thoracic duct, lymphatics, microarray Four unique thoracic duct/vena cava sample pairs were individually analyzed via two-color microarray analysis yielding 4 biological replicates. To minimize dye bias, a dye balance design was utilized in which the orientation of dye assignment was alternated between vessel pairs (i.e. two thoracic duct samples were labeled with Cy3 and two were labeled with Cy5). Prior to analysis, the data from 2 of the replicates was transformed to accomodate the dye balance such that all thoracic duct data is interpreted as Cy5 and all vena cava data is interpreted as Cy3.
2010-05-15 | E-GEOD-7221 | biostudies-arrayexpress
Project description:While blood vessels have muscular walls that undergo tonic contractions to alter vascular resistance and, thus, control blood flow, lymphatics at the level of the collecting vessels and higher have muscular walls capable of rapid phasic contractions that generate lymph flow in addition to tonic contractions that regulate lymph flow resistance. While the ability of lymphatics to undergo rapid phasic contractions has been known for several centuries, the biological elements governing this phenomenon remain unknown. In an attempt to gain insight into the structural and regulatory elements that give lymphatic vessels their unique contractile capabilities, we utilized two-color microarray analysis to compare the thoracic duct of the rat to the vena cava of the same donor animal. Total cellular RNA was isolated immediately following vessel isolation and amplified in the presence of amino allyl dUTP. The resulting modified aRNA was conjugated to either Cy3 or Cy5 dye prior to hybridization to a rat 5.7K oligonucleotide array. Analysis and filtering of the data obtained from the microarray image yielded several contractile and regulatory genes with altered expression in the thoracic duct relative to the vena cava. Further evaluation of the data obtained in this study may aid in illustrating the unique properties of the lymphatic vessel and its muscular wall. Keywords: Thoracic duct, lymphatics, microarray
2010-01-27 | GSE7221 | GEO