Formation and segregation of cell lineages forming the heart have been studied extensively but the underlying gene regulatory networks and epigenetic changes driving cell fate transitions during early cardiogenesis are still only partially understood. Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq). By leveraging on cell-to-cell transcriptome and chromatin accessibility heterogeneity, we identify different previously unknown cardiac subpopulations. Reconstruction of developmental trajectories reveal that multipotent Isl1+ CPC pass through an attractor state before separating into different developmental branches, whereas extended expression of Nkx2-5 commits CPC to an unidirectional cardiomyocyte fate. Furthermore, we show that CPC fate transitions are associated with distinct open chromatin states critically depending on Isl1 and Nkx2-5. Our data provide a model of transcriptional and epigenetic regulations during cardiac progenitor cell fate decisions at single-cell resolution.
Identification of genes periodically expressed in the human cell cycle and their expression in tumors
Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart
Hoxa3 regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice
Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart
Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification
An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation
Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities
The molecular and mathematical basis of Waddington's epigenetic landscape: a framework for post-Darwinian biology?
miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development
Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position
Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression during reprogramming
Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development
MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data
Transcriptomic Profiling Maps Anatomically Patterned Subpopulations among Single Embryonic Cardiac Cells
Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells
Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation
Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation
Matrix factorization and transfer learning uncover regulatory biology across multiple single-cell ATAC-seq data sets.
Trajectory mapping of human embryonic stem cell cardiogenesis reveals lineage branch points and an ISL1 progenitor-derived cardiac fibroblast lineage
Erratum: DeconPeaker, a Deconvolution Model to Identify Cell Types Based on Chromatin Accessibility in ATAC-Seq Data of Mixture Samples
Transcriptional Profiling of CD8+ CMV-Specific T Cell Functional Subsets Obtained Using a Modified Method for Isolating High-Quality RNA From Fixed and Permeabilized Cells.
Expression of smooth muscle-like effectors and core cardiomyocyte regulators in the contractile papillae of Ciona
ATAC-seq normalization method can significantly affect differential accessibility analysis and interpretation.
H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts.
Biological and Medical Importance of Cellular Heterogeneity Deciphered by Single-Cell RNA Sequencing.
Epigenetics Analysis and Integrated Analysis of Multiomics Data, Including Epigenetic Data, Using Artificial Intelligence in the Era of Precision Medicine
DeconPeaker, a Deconvolution Model to Identify Cell Types Based on Chromatin Accessibility in ATAC-Seq Data of Mixture Samples
UniPath: a uniform approach for pathway and gene-set based analysis of heterogeneity in single-cell epigenome and transcriptome profiles.
Cardiac endothelial cells maintain open chromatin and expression of cardiomyocyte myofibrillar genes.
Cell-Type-Specific Gene Regulatory Networks Underlying Murine Neonatal Heart Regeneration at Single-Cell Resolution.
FITs: forest of imputation trees for recovering true signals in single-cell open chromatin profiles.
BMP2-dependent gene regulatory network analysis reveals Klf4 as a novel transcription factor of osteoblast differentiation.
Ex uno, plures-From One Tissue to Many Cells: A Review of Single-Cell Transcriptomics in Cardiovascular Biology.
Bench-to-Bedside in Vascular Medicine: Optimizing the Translational Pipeline for Patients With Peripheral Artery Disease.
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