Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bmi1 defines long-term adult cardiac stem cells in heart homeostasis and repair

ABSTRACT: We have found the existence of a Bmi1+ population in the adult heart contributing to the organ low-rate turnover and repair with the generation of new cardiomyocytes. We show that the Bmi1+ population is a sub-population of the cardiac Sca-1+ progenitor cells. We have analyzed the gene profile by deep-sequencing (RNA-Seq) of Bmi1+ and Sca-1+Bmi1- cells in homeostatic heart condition. On the other hand, we have compared gene profile by deep-sequencing (RNA-Seq) of Bmi1+ cells in homeostatic condition versus Bmi1+ cells 5 days after myocardial infarction (MI). Analysis of RNA-Seq data revealed a differential expression signature between both subsets of cardiac stem/progenitors cells in homeostatic condition and also differences between Bmi1+ cells after AMI versus homeostatic condition.

ORGANISM(S): Mus musculus

PROVIDER: GSE55754 | GEO | 2017/02/14

SECONDARY ACCESSION(S): PRJNA240889

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single cell RNA sequencing of Hic1 and PDGFRa-labeled cells in the heart

Project description:The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are poorly defined. Here, we identify heart-resident PDGFRa+ SCA-1+ cells as cardiac Fibro/Adipogenic Progenitors (cFAPs) and show that they respond to ischemic damage by generating SCA-1- fibrogenic cells. Pharmacological blockade of this differentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardial infarction (MI) remodeling and leads to improvement in heart function.

2020-01-23 | GSE141928 | GEO

Transcriptional profile of PDGFRa+ Sca-1+ and Sca-1- cells at steady state and at 7, 14 and 28 days post LAD ligation

2020-01-23 | GSE141927 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 4; Bmi1-deficient)

Project description:Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline in geriatric satellite cells, compared to old cells are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and this irreversibly affects their intrinsic regenerative and self-renewal capacities. In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16INK4a. Young Bmi1-deficient satellite cells shares similar features. We analyzed the global changes in gene expression occurring within muscle stem cells (satellite cells) in homeostatic conditions during physiological aging. Pure satellite cell populations from dissociated skeletal muscle from WT and Bmi1-deficient mice were isolated using a well-established flow cytometry protocol gating on integrin a7(+)/CD34(+) (positive selection) and Lin- (CD31, CD45, CD11b, Sca1) (negative selection).

2013-12-31 | E-GEOD-53727 | biostudies-arrayexpress

Brain-derived neurotrophic factor contributes to the cardiogenic potential of adult resident progenitor cells in failing murine heart

Project description:Aims: Resident cardiac progenitor cells show homing properties when injected into the injured but not into the healthy myocardium. The molecular background behind this difference in behavior needs to be studied to elucidate how adult progenitor cells can restore cardiac function of the damaged myocardium. Since the brain-derived neurotrophic factor (BDNF) moderates cardioprotection in injured hearts, we focused on delineating its regulatory role in the damaged myocardium. Methods and Results: Comparative gene expression profiling of freshly isolated undifferentiated Sca-1 progenitor cells derived either from heart failure transgenic αMHC-CyclinT1/Gαq overexpressing mice or wildtype littermates revealed transcriptional variations. Bdnf expression was up-regulated 5-fold during heart failure, which was verified by qRT-PCR and confirmed at the protein level. The migratory capacity of Sca-1 cells from transgenic heart was improved by 15% in the presence of 25ng/ml BDNF. Furthermore, BDNF-mediated effects on Sca-1 cells were studied via pulsed Stable Isotope Labeling of Amino acids in Cell Culture (pSILAC) proteomics approach. After BDNF treatment, significant differences between newly synthesized proteins in Sca-1 cells isolated from control and transgenic mice were observed for CDK1, SRRT, HDGF, and MAP2K3, which are known to regulate cell cycle, survival and differentiation. Moreover, BDNF repressed the proliferation of Sca-1 cells from transgenic hearts. Conclusion: Comparative profiling of resident Sca-1 cells revealed elevated BDNF levels in the failing heart. Exogenous BDNF (i) stimulated migration, which might improve the homing ability of Sca-1 cells derived from the failing heart and (ii) repressed the cell cycle progression suggesting its potency to ameliorate heart failure.

2015-03-26 | GSE58577 | GEO

Project description:The accumulation of reactive oxygen species (ROS) is linked to several cardiovascular pathologies; it is also associated with cell cycle exit by nenonatal cardiomyocytes, a key limiting factor in the regenerative capacity of the adult mammalian heart. BMI1 is a component of the polycomb complex 1, which is linked to adult multipotent progenitors, and is also an important partner in DNA repair and redox regulation. Here we show that high BMI1 expression is associated with a cardiac Sca1+ progenitor subpopulation with low ROS levels. In homeostasis, BMI1 represses cell-fate genes, including a cardiogenic differentiation program. Persistent oxidative damage nonetheless modified BMI1 activity in vivo, by derepressing canonical target genes in favor of their antioxidant and anticlastogenic functions. This derepression induced cardiac progenitor proliferation and differentiation, and thus increased its contribution to mature cardiac progeny. This redox-mediated mechanism is not restricted to damage situations, and we report ROS-associated differentiation of cardiac progenitors in steady state. These findings demonstrate how redox status influences the adult cardiac progenitor response, and identifies a redox-mediated BMI1 function with potential implications in adult cardiac turnover.

2018-01-01 | GSE92700 | GEO

Loss of Cardiac microRNA-Mediated Regulation Leads to Dilated Cardiomyopathy and Heart Failure.

Project description:RATIONALE: Heart failure is a deadly and devastating disease that places immense costs on an aging society. To develop therapies aimed at rescuing the failing heart, it is important to understand the molecular mechanisms underlying cardiomyocyte structure and function. OBJECTIVE: microRNAs are important regulators of gene expression, and we sought to define the global contributions made by microRNAs toward maintaining cardiomyocyte integrity. METHODS AND RESULTS: First, we performed deep sequencing analysis to catalog the miRNA population in the adult heart. Second, we genetically deleted, in cardiac myocytes, an essential component of the machinery that is required to generate miRNAs. Deep sequencing of miRNAs from the heart revealed the enrichment of a small number of microRNAs with one, miR-1, accounting for 40% of all microRNAs. Cardiomyocyte-specific deletion of dgcr8, a gene required for microRNA biogenesis, revealed a fully penetrant phenotype that begins with left ventricular malfunction progressing to a dilated cardiomyopathy and premature lethality. CONCLUSIONS: These observations reveal a critical role for microRNAs in maintaining cardiac function in mature cardiomyocytes and raise the possibility that only a handful of microRNAs may ultimately be responsible for the dramatic cardiac phenotype seen in the absence of dgcr8. We report the miRNA composition of 6-8 week old murine heart. We performed deep sequencing analysis to catalog the miRNA population in the adult heart. 2 sample were sequenced.

2011-10-11 | E-GEOD-32881 | biostudies-arrayexpress

Foxa2 identifies a novel ventricular-specific cardiac progenitor population during gastrulation.

Project description:The recent identification of novel progenitor populations that contribute to the developing heart in a distinct temporal and spatial manner has fundamentally improved our understanding of cardiac development. However, little remains known about cardiac specification events prior to the establishment of the heart tube, or the mechanisms that direct atrial versus ventricular specification. We have identified a novel progenitor population that gives rise specifically to cardiovascular cells of the ventricles but not the atria, and to the epicardium of the differentiated heart. We determined that this cell population is first specified during gastrulation, when it transiently expresses Foxa2, a gene not previously implicated in cardiac development. Using chimeric mosaic analysis we further demonstrate that Foxa2 is cell-autonomously required for the development of ventricular cells. Finally, we reveal the existence of an analogous Foxa2+ cardiac mesoderm population during in vitro differentiation from embryonic stem cells and illustrate that these cells express genes relevant for heart development. Our data thus describe the first progenitor population identified as early as gastrulation that displays ventricular-specific differentiation potential. Together, these findings provide important new insights into the developmental origin of ventricular and atrial myocytes, and will lead to the establishment of new strategies for generating these cell types from pluripotent stem cells.

2017-02-08 | GSE78964 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and cardiac-specific Bmi1 deletion [mouse]

Project description:To explore the primary cause of Dilated Cardiomyopathy in Bmi1-null mice, we set out to identify differentially expressed genes by massively parallel sequencing of heart samples from Bmi1f/f;?MHCTM-Cretg/+ mice versus ?MHCTM-Cretg/+ control mice (17 weeks postinduction). Methods: Heart mRNA profiles of 17-weeks post-induction Bmi1f/f; MHCTM-Cretg/+ mice and MHCTM-Cretg/+ control mice were generated by deep sequencing, in triplicate, using Illumina GAIIx. Sequence reads were pre-processed with Cutadapt 1.2.1, to remove TruSeq adapters and mapped on the mouse transcriptome (Ensembl gene-build GRCm38.v70) using RSEM v1.2.3. The Bioconductor package EdgeR was used to normalize data with TMM and to test for differential expression of genes using GLM.

2015-01-13 | E-GEOD-64391 | biostudies-arrayexpress

Single-cell analysis revealed the role of CD8+ effector T cells in preventing cardioprotective macrophage differentiation in the early phase of heart failure

Project description:In this study, we explore a dynamic interplay between cardiac CD8+T cells and macrophages that is necessary for adaptation to cardiac stress, highlighting the homeostatic functions of resident and infiltrated macrophages in the heart. To understand transcriptomic differences of the heart, we performed single-cell RNA sequencing (scRNA-seq) analysis on cardiomyocytes.

2021-09-05 | GSE183405 | GEO

Heart-resident PDGFRa+ SCA-1+ cells

Project description:Heart-resident PDGFRa+ SCA-1+ cells

| PRJNA595180 | ENA