Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lysophosphatidic Acid Receptor 4 is transiently expressed during cardiac differentiation and critical for repair of the damaged heart

ABSTRACT: Efficient differentiation of pluripotent stem cells (PSCs) into cardiac cells is essential for the development of new therapeutic modalities to repair damaged heart tissue. We identified a novel cell surface marker, the G protein-coupled receptor lysophosphatidic acid receptor 4 (LPAR4), specific to cardiac progenitor cells (CPCs) and determined its functional significance and therapeutic potential. During in vitro differentiation of mouse and human PSCs toward cardiac lineage, LPAR4 expression peaked after 3−7 days of differentiation in cardiac progenitors and then declined. In vivo, LPAR4 was specifically expressed in the early stage of embryonal heart development, and as development progressed, LPAR4 expression decreased and was non-specifically distributed. We identified the effective agonist octadecenyl phosphate and a p38 MAPK blocker, as the downstream signal blocker. Sequential stimulation and inhibition of LPAR4 using these agents enhanced the in vitro efficiency of cardiac differentiation from mouse and human PSCs. Importantly, in vivo, this sequential stimulation and inhibition of LPAR4 reduced the infarct size and rescued heart dysfunction in mice. In conclusion, LPAR4 is a novel CPC marker transiently expressed only in heart during embryo development. Modulation of LPAR4-positive cells may be a promising strategy for repairing myocardium after myocardial infarction.

ORGANISM(S): Mus musculus

PROVIDER: GSE83434 | GEO | 2016/06/17

SECONDARY ACCESSION(S): PRJNA325923

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of Latrophilin-2, a Specific Cell-surface Marker for Cardiac Progenitor Cells, and its Functional Significance in Heart Development [RNA-Seq]

Project description:Background: Identification of a lineage-specific marker plays a pivotal role in understanding developmental process and is necessary to isolate a certain cell type with high purity for therapeutic purposes. Here, we report a new cardiac-specific marker and demonstrate its functional significance in cardiac development. Methods: When mouse pluripotent stem cells (PSCs) were stimulated with BMP4, Activin A, and bFGF, they differentiated into cardiac cells. To screen molecules expressed on cardiac progenitor cell (CPC) surfaces compared to those on undifferentiated PSCs, we isolated Flk1+/PdgfRa+ cells at differentiation day 4 and performed microarray analysis. Results: Among candidates, we identified a new G protein-coupled receptor, latrophilin-2 (Lphn2). Here, we report this new cardiac-specific surface marker, Lphn2, expressed specifically on CPCs and cardiomyocytes (CMCs) during mouse and human PSC differentiation in vitro and exclusively in the heart during mouse embryonic development. Lphn2 knockout in mice was embryonically lethal because of severe heart, but not vascular, defects. PSC-derived Lphn2+ cells, but not Lphn2- cells, differentiated into CMCs and regenerated the myocardium when transplanted into infarcted hearts. Transplanted Lphn2+ cells improved left ventricular systolic function and reduced infarct sizes. Analysis of the signaling pathway indicated that cyclin-dependent kinase 5 is downstream of Lphn2 and collaborates with Src kinase to induce P38MAP kinase phosphorylation, subsequently activating cardiac-related gene transcription. Conclusion: Lphn2 is a functionally significant cell-surface marker for cardiac progenitor and cardiomyocytes. These findings provide a valuable tool for isolating cardiomyogenic progenitors and CMCs from PSCs and shed light on heart development and regeneration.

2018-12-31 | GSE102973 | GEO

Single-cell transcriptomic analysis reveals lineage hierarcies and communications for second heart lineage deployment [RNA-seq]

Project description:We used single-cell RNA-seq to reconstruct differentiation paths of cardiac progenitors in two sequential waves during early heart development. Further analysis identified six major cell types and multiple differentiation trajectories of cardiac progenitors derived from distinct heart fields. We also constructed TF regulatory networks controlling SHF CPC differentiation. Interlineage crosstalk through signaling pathways and chemotactic guidance played a potent role in SHF CPC deployment. The mechanisms regulating SHF CPC migration and differentiation was further confirmed by Nkx2-5 CPC enhancer knock out. Our work provides a cardiac lineage hierarchy and new insights of SHF CPC development.

2019-06-22 | GSE108879 | GEO

Single-cell transcriptomics reveals chemotaxis mediated intra-organ crosstalk during cardiogenesis [ChIP-seq]

Project description:We used single-cell RNA-seq to reconstruct differentiation paths of cardiac progenitors in two sequential waves during early heart development. Further analysis identified six major cell types and multiple differentiation trajectories of cardiac progenitors derived from distinct heart fields. We also constructed TF regulatory networks controlling SHF CPC differentiation. Interlineage crosstalk through signaling pathways and chemotactic guidance played a potent role in SHF CPC deployment. The mechanisms regulating SHF CPC migration and differentiation was further confirmed by Nkx2-5 enhancer knock out. Our work provides a cardiac lineage hierarchy and new insights into SHF CPC development. Mechanistically, NKX2-5 directly bound the Cxcr2 genomic locus and activated its transcription.

2019-06-22 | GSE108961 | GEO

Adhesion GPCR, latrophilin-2, specifies cardiac lineage commitment through CDK5, Src, and P38MAPK

Project description:Identifying lineage-specific markers is pivotal for understanding developmental processes and developing cell therapies. Here, we report a new cardiomyogenic cell surface marker latrophilin-2 (Lphn2), an adhesion G protein-coupled receptor. When mouse and human pluripotent stem cells (PSCs) were stimulated with BMP4, Activin A, and bFGF, they differentiated into cardiac lineage cells. Lphn2 was selectively expressed on cardiac progenitor cells (CPCs) and cardiomyocytes (CMCs) during the differentiation of mouse PSCs, and cell sorting with an anti-Lphn2 antibody promoted the isolation of populations highly enriched in CPCs and CMCs. Lphn2 knock-down or knock-out PSCs did not express cardiac genes. To investigate the molecular mechanism underlying the induction of cardiac differentiation by Lphn2, we used the Phospho Explorer Antibody Array, which encompasses nearly all known signaling pathways. Lphn2-dependent phosphorylation was strongest for cyclin-dependent kinase 5 (CDK5) at Tyr15. We identified CDK5, Src, and P38MAPK as key downstream molecules of Lphn2. These findings provide a valuable tool for isolating cardiomyogenic progenitors and CMCs from PSCs and shed light on the still-unknown mechanisms of cardiac differentiation.

2017-01-06 | GSE92923 | GEO

Gene expression changes in beta-blocker treated neonatal hearts

Project description:The regeneration potential of the mammalian heart is limited. We found that treatment of beta-blocker robustly enhanced cardiomyocyte proliferation and promoted cardiac regeneration post myocardial infarction. To investigate the gene expression changes, we performed RNA-seq using the hearts treated with beta-blocker for 7 days.

2022-08-30 | GSE186099 | GEO

Functional Cardiac Fibroblasts Derived from Human Pluripotent Stem Cells via Second Heart Field Progenitors

Project description:Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties (EP) of the cardiomyocytes compared to co-culture with dermal fibroblasts (DFs). The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration.

2019-02-08 | GSE126260 | GEO

Parthenogenetic stem cells for tissue-engineered heart repair

Project description:Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair. 8 samples in total. Parthenogenetic stem cells (PSC): - PSC_1 - PSC_2 - PSC_3 Embryoid body (EB) assays of parthenogenetic stem cells: - EB_PSC_1 - EB_PSC_2 Embryonic stem cells (ESC): - ESC_1 - ESC_2 - ESC_3

2013-02-23 | E-GEOD-30868 | biostudies-arrayexpress

Sequential defects in cardiac lineage commitment and maturation cause hypoplastic left heart syndrome

Project description:Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most severe congenital heart defect encompassing a spectrum of left-ventricular hypoplasia occurring in association with outflow-tract obstruction. The current clinical paradigm assumes HLHS is largely of hemodynamic origin. Here, by combining whole-exome sequencing of 87 HLHS parent-offspring trios and transcriptome of cardiomycytes (CMs) from healthy and patient native ventricles at different stages of development we identified perturbations in coherent gene programs controlling ventricular muscle lineage development. Single-cell and 3D molecular/functional modeling with iPSCs demonstrated intrinsic defects in the cell-cycle/ciliogenesis/autophagy hub resulting in disrupted differentiation of early cardiac progenitor (CP) lineages and ultimate defective CM-subtype differentiation/maturation in HLHS. Moreover, premature cellcycle exit of ventricular CM prevents tissue response to cues of developmental growth leading to multinucleation/polyploidy, accumulation of DNA damage, exacerbated apoptosis, and eventually ventricle hypoplasia. Our results highlight how genetic heterogeneity in HLHS converges in perturbations of sequential cellular processes driving cardiogenesis and facilitate potential novel nodes for therapy beside surgical intervention.

2022-02-15 | PXD014812 | Pride

Induction of circular RNA in fetal heart development recapitulated in in vitro differentiation

Project description:We discovered induction of circular RNA in human fetal tissues, including the heart. In this study, we were able to recapitulate this induction by in vitro directed differentiation of hESCs to cardiomyocytes, paving the way for future studies into circular RNA regulation. We harvested hESCs at sequential stages of differentiation: undifferentiated (day 0), mesoderm (day 2), cardiac progenitor (day 5) and definitive cardiomyocyte (day 14). We performed RNA sequencing in biological triplicate, with 3-8 technical replicates each.

2015-06-25 | E-GEOD-64417 | biostudies-arrayexpress

Synaptic Schwann cells: specific labeling reveals unique cellular and molecular features

Project description:Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100β+ PSCs in skeletal muscle. NG2 is expressed in Schwann cells already associated with the NMJ, indicating that it is a marker of differentiated PSCs. Using a newly generated transgenic mouse in which PSCs are specifically labeled, we show that PSCs have a unique molecular signature that includes genes known to play critical roles in PSCs and synapses. These findings will serve as a springboard for revealing drivers of PSC differentiation and function.

2020-06-19 | GSE152774 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data