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EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196516 | GEO | 2023/02/04

REPOSITORIES: GEO

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Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease.

Project description:The epicardium, the mesothelial envelope of the vertebrate heart, is the source of multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth and repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids that display retinoic acid-dependent morphological, molecular and functional patterning of the epicardium and myocardium typical of the left ventricular wall. By combining lineage tracing, single-cell transcriptomics and chromatin accessibility profiling, we describe the specification and differentiation process of different cell lineages in epicardioids and draw comparisons to human fetal development at the transcriptional and morphological levels. We then use epicardioids to investigate the functional cross-talk between cardiac cell types, gaining new insights into the role of IGF2/IGF1R and NRP2 signaling in human cardiogenesis. Finally, we show that epicardioids mimic the multicellular pathogenesis of congenital or stress-induced hypertrophy and fibrotic remodeling. As such, epicardioids offer a unique testing ground of epicardial activity in heart development, disease and regeneration.

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EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE [scRNA-Seq]

Project description:Native human epicardial precursors are virtually inaccessible, as they appear in the embryo less than four weeks post-conception, at which point pregnancy may not yet be detected. Protocols have been established to generate epicardial cells and their progeny from human pluripotent stem cells in vitro. However, no current model is amenable to studying the many facets of human epicardial biology, notably epicardium formation, lineage heterogeneity, and functional crosstalk with other cardiac cell types during organ development and disease. Here, we generated human pluripotent stem cell-derived 3D heart organoids showing retinoic acid-dependent self-organization of the epicardium and myocardium, which we called epicardioids. Time course single-cell RNA sequencing revealed that epicardioids are formed through the specification of first heart field progenitors, a subset of which closely correspond to juxta-cardiac field (JCF) cells that have recently been identified in the embryonic mouse heart as novel common progenitors of myocardium and epicardium and have not yet been described and studied in humans. Analysis of chromatin accessibility by single-cell ATAC-seq additionally revealed key transcriptional programs guiding fate decisions along the epicardial lineage tree. Human epicardioids provide a unique model to gain fundamental insights into human epicardium biology and function during heart development, homeostasis, and disease.

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EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE [scATAC-Seq]

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EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE

Project description:EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE

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EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE [scATAC-Seq]

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EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE [scRNA-Seq]

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Engineered cell entry links receptor biology with single-cell genomics

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description: Not available

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