Hapln1 defines an epicardial cell subpopulation that establishes cardiogenic hotspots during heart morphogenesis and regeneration
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ABSTRACT:
PROVIDER: PRJNA723588 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14295679_1.fastq.gz | Fastqsanger.gz | |||
| SRR14295679_2.fastq.gz | Fastqsanger.gz | |||
| SRR14295680_1.fastq.gz | Fastqsanger.gz | |||
| SRR14295680_2.fastq.gz | Fastqsanger.gz |
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Project description:The epicardium, a thin mesothelial tissue layer that encompasses the heart, is a dynamic structure that is essential for cardiac regeneration in species with elevated regenerative capacity like zebrafish. To dissect epicardial cell states and associated pro-regenerative functions, we performed single-cell RNA-sequencing and identified 7 epicardial cell clusters in adult zebrafish, with 3 of these clusters enhanced during regeneration. ECM components encoded by hapln1 paralogs label an enriched epicardial cell type that accumulates and encloses dedifferentiated and proliferating cardiomyocytes during regeneration. Genetic inactivation of hapln1b, or induced genetic depletion of hapln1a-expressing cells, disrupted cardiomyocyte proliferation and heart regeneration. hapln1a+ cells first emerge at the juvenile stage, when they associate with and are required for cardiogenic foci that direct growth of the juvenile heart. Our findings identify a subset of epicardial cells that emerges in post-embryonic animals and sponsors regions of active cardiomyogenesis during heart growth and regeneration
2022-06-17 | GSE172511 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis. Bioinformatic analysis showed that HAPLN1 expression is enriched in the basal PDAC subtype and associated with worse overall patient survival. In a mouse model for peritoneal carcinomatosis, HAPLN1-induced immunomodulation favored a more permissive microenvironment, which accelerated the peritoneal spread of tumor cells. Mechanistically, HAPLN1, via upregulation of tumor necrosis factor receptor 2 (TNFR2), promoted TNF-mediated upregulation of Hyaluronan (HA) production, facilitating EMT, stemness, invasion and immunomodulation. Extracellular HAPLN1 modified cancer cells and fibroblasts, rendering them more immunomodulatory. As such, we identified HAPLN1 as a prognostic marker and as a driver for peritoneal metastasis in PDAC.
2023-03-31 | GSE211126 | GEO
Project description:To investigate the role of HAPLN1 in multiple myeloma, we treated RPMI8226 multiple myeloma cells with recombinant HAPLN1-PTR1. We then performed gene expression profiling analysis using data obtained from RNA-seq.
2022-09-06 | GSE202672 | GEO
Project description:BackgroundCertain nonmammalian species such as zebrafish have an elevated capacity for innate heart regeneration. Understanding how heart regeneration occurs in these contexts can help illuminate cellular and molecular events that can be targets for heart failure prevention or treatment. The epicardium, a mesothelial tissue layer that encompasses the heart, is a dynamic structure that is essential for cardiac regeneration in zebrafish. The extent to which different cell subpopulations or states facilitate heart regeneration requires research attention.MethodsTo dissect epicardial cell states and associated proregenerative functions, we performed single-cell RNA sequencing and identified 7 epicardial cell clusters in adult zebrafish, 3 of which displayed enhanced cell numbers during regeneration. We identified paralogs of hapln1 as factors associated with the extracellular matrix and largely expressed in cluster 1. We assessed HAPLN1 expression in published single-cell RNA sequencing data sets from different stages and injury states of murine and human hearts, and we performed molecular genetics to determine the requirements for hapln1-expressing cells and functions of each hapln1 paralog.ResultsA particular cluster of epicardial cells had the strongest association with regeneration and was marked by expression of hapln1a and hapln1b. The hapln1 paralogs are expressed in epicardial cells that enclose dedifferentiated and proliferating cardiomyocytes during regeneration. Induced genetic depletion of hapln1-expressing cells or genetic inactivation of hapln1b altered deposition of the key extracellular matrix component hyaluronic acid, disrupted cardiomyocyte proliferation, and inhibited heart regeneration. We also found that hapln1-expressing epicardial cells first emerge at the juvenile stage, when they associate with and are required for focused cardiomyocyte expansion events that direct maturation of the ventricular wall.ConclusionsOur findings identify a subset of epicardial cells that emerge in postembryonic zebrafish and sponsor regions of active cardiomyogenesis during cardiac growth and regeneration. We provide evidence that, as the heart achieves its mature structure, these cells facilitate hyaluronic acid deposition to support formation of the compact muscle layer of the ventricle. They are also required, along with the function of hapln1b paralog, in the production and organization of hyaluronic acid-containing matrix in cardiac injury sites, enabling normal cardiomyocyte proliferation and muscle regeneration.
| S-EPMC9308751 | biostudies-literature
Project description:Rationale: Epicardium-derived cells (EPDC) are formed in response to myocardial infarction and recapitulate an embryonic program that is likely to participate in cardiac regeneration and remodeling. The existence of atrial counterparts that are potentially involved in atrial remodeling is still elusive. Objective: We have elaborated and validated techniques for the robust isolation and cultivation of atrial and ventricular EPDC from the rat heart and compared their molecular phenotype with human atrial stromal cells obtained from tissue biopsies. Methods and Results: In vitro culture revealed that rat and human cells display a similar morphology, are highly enriched for the epicardial markers WT-1 and Tbx18 throughout in vitro expansion, strongly express the stem/progenitor cell markers CD73, CD90 and, surprisingly the early and late cardiac markers Gata4, Tbx5 and troponin T. In general, these cells display a similar molecular signature - which is different from human MSC - when analyzed by FACS, immunohistochemistry and real time PCR. We also examined the cell surface proteome of human and rat EPDC using cell surface biotinylation combined with nano-liquid chromatography - mass spectrometry. Proteome analysis revealed the presence of 149 overlapping proteins and >200 species specific proteins. These proteins are preferentially involved in cardiac repair and regeneration. Conclusions: This study demonstrates that atrial stromal cells are EPDC suggesting a common epicardial precursor. Cell surface proteome analysis suggests that atrial and ventricular EPDC are likely to play an important role during atrial and ventricular remodeling.
2018-10-19 | PXD005013 | Pride
Project description:To identify the HAPLN1-induced genes regulated by STAT1 in multiple myeloma, we treated RPMI8226 multiple myeloma cells (WT or STAT1 KO) with recominant HAPLN1-PTR1. We then performed gene expression profiling analysis using data obtained from RNA-seq.
2023-12-06 | GSE237216 | GEO
Project description:Objectives: HAPLN1 stabilize the macromolecular structure of the extracellular matrix (ECM) and its expression is increased in a few types of musculoskeletal diseases including rheumatoid arthritis (RA). However, its functions are obscure. Methods: Here, how HAPLN1 contributes to the viability, proliferation, mobility and pro-inflammatory phenotype of RA-FLSs was investigated using small interfering RNA (siHAPLN1), over-expression vector (HAPLN1OE) and a recombinant HAPLN1 (rHAPLN1) protein. Results: Interestingly, HAPLN1 promoted proliferation but inhibited migration of RA-FLSs. Earlier we reported the function of metformin, an AMPK activator, in the inhibition of FLSs activation but promotion of HAPLN1 secretion. In this study, we confirmed the findings of up-regulated HAPLN1 in RA patients, and it is positively correlated with AMPK. Both si-HAPLN1 and HAPLN1OE treatment has down-regulated the expression of AMPK-ɑ gene but the levels of phosphorylated AMPK-ɑ were found to be up-regulated in RA-FLSs. Furthermore, si-HAPLN1 had down-regulated the gene and protein expression of proinflammatory factors like TNF-ɑ, MMPs and IL-6, while HAPLN1OE up-regulated their levels. qPCR assay also indicated down regulated TGF-β, ACAN, Fibronectin, collagen Ⅱ, and Ki-67 by si-HAPLN1 treatment, while up-regulated ACAN, Ki-67 and down regulated cyclin-D1 by HAPLN1OE treatment. Proteomics of si-HAPLN1, rHAPLN1 and mRNA-Seq analysis of rHAPLN1 confirmed the functions of HAPLN1 in the activation of inflammation, proliferation, increased cell adhesion, and strengthening of ECM function. Conclusions: Collectively, these findings demonstrate HAPLN1 function in promoting proliferation and pro-inflammatory phenotype of RA-FLSs, which in turn could contribute to RA pathogenesis.
2022-06-22 | GSE200597 | GEO
Project description:The epicardium is a mesothelial layer covering the myocardium and contributes to different cardiac lineage descendants during cardiogenesis. Fine-tuned balanced signaling defines epicardial specification and regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) by epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial cell function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated embryonic epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a novel biomarker defining lineage specification in human developing epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results demonstrate the production and enrichment of hiPSC-derived epicardial cells via the tracing of CDH18 expression, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine.
2022-02-18 | GSE165450 | GEO
Project description:Single cell RNA sequencing (scRNA-Seq) is applied to charaterize the pro-epicardial cells (proEpiCs) in mouse pro-epicardial organ (PEO).
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