Population and Single-Cell Analysis of Human Cardiogenesis Reveals Unique LGR5 Ventricular Progenitors in Embryonic Outflow Tract

Sahara, Makoto; Santoro, Federica; Sohlmér, Jesper; Zhou, Chikai; Witman, Nevin; Leung, Chuen Yan; Mononen, Mimmi; Bylund, Kristine; Gruber, Peter J.; Chien, Kenneth R.

doi:10.1016/j.devcel.2019.01.005

Cited by 79 publications

(108 citation statements)

References 49 publications

(80 reference statements)

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…Future studies should determine if this occurs with this common human coding variant of C5ORF46. Prior studies have identified links between C5ORF46 and either heart disease, or heart development (46,47). This agrees with the expression profile in human tissues and cells, where C5ORF46 is detectable at the RNA-level in major blood vessels (aorta) and the heart, but also in skin and salivary gland ( Fig.…”

Section: E G S D K N P E K P D E K P a D S G K S P E K P D D K P D D supporting

confidence: 86%

Small-protein Enrichment Assay Enables the Rapid, Unbiased Analysis of Over 100 Low Abundance Factors from Human Plasma

Harney

Hutchison

et al. 2019

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Small proteins in plasma regulate diverse processes from metabolism to immune functions and are difficult to study, because of the large dynamic range of protein abundance. To facilitate their detection, we developed a method using protein dissociation, precipitation and size exclusion chromatography called SPEA. Herein, we demonstrate SPEA is capable of reproducible characterization of known small proteins and identification of novel factors such as C5ORF46. When applied to study humans undergoing intermittent fasting, novel changes in iron regulation were observed.

show abstract

Section: E G S D K N P E K P D E K P a D S G K S P E K P D D K P D D supporting

confidence: 86%

Small-protein Enrichment Assay Enables the Rapid, Unbiased Analysis of Over 100 Low Abundance Factors from Human Plasma

Harney

Hutchison

et al. 2019

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…Isl1 has a well-established role in mammalian cardiac development and is expressed in multipotent cardiovascular progenitor cells in mice [39][40][41] and humans [42,43]. Despite its established role in heart development in mice, loss of function variants in the ISL1 locus are drastically underrepresented in large human cohorts of congenital heart malformations like the Pediatric Cardiac Genomics Consortium (PCGC) [28,44].…”

Section: Discussionmentioning

confidence: 99%

Amnion signals are essential for mesoderm formation in primates

Yang

Goedel

Kang

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The signaling network governing the formation of the primitive streak is well understood in mice, but largely unexplored in primates. Advances in single-cell technology and in vitro embryo culture have enabled to characterize the major cell populations involved. However, a detailed map of this process and insights into its regulatory networks are lacking. Herein, we generated a serial single cell atlas of over 30,000 cells spanning peri-implantation to early primitive streak stages in non-human primates (NHP) describing the emergence of the primitive streak, extraembryonic mesenchyme and amnion. We discovered that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amniotic cells. Strikingly, CRISPR/Cas9-targeting of ISL1 resulted in NHP embryos failing to form primitive streak. BMP4 was identified as a key signaling pathway in this process. This was confirmed in human embryonic stem cell lines, suggesting a conserved function in humans. Notably, no viable ISL1 hypomorphic NHP mutant embryos could be recovered after embryo transfer confirming the essential requirement of ISL1. This highlights the importance of the amnion as a signaling center during primate embryogenesis and demonstrates the potential of in vitro primate model systems to investigate the genetics of early human development.

show abstract

“…Additionally, GINS3 is enriched in these cells, which is known to participate in the regulation of cardiac repolarization 71,72 . NC3 and NC4 subpopulations shared a broadly similar transcriptional profile including LGR5 , a G-protein-coupled receptor involved in Wnt -signaling that promotes CM differentiation 73 and demarcates a subset of CM in the outflow tract 74 ; this region often becomes arrhythmogenic in heart disease 75 . These cells also expressed genes associated with coronary artery disease, PPP2R2B 76 , LSAMP 77 and LPL an endothelial enzyme involved transporting lipoproteins into the heart 78 .…”

Section: Nc1 Was Distinguished By Enriched Expression Ofmentioning

confidence: 99%

Cells and gene expression programs in the adult human heart

Litviňuková

Talavera-López

Maatz

et al. 2020

Preprint

View full text Add to dashboard Cite

SummaryCardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and strategies to improve therapeutic opportunities require deeper understanding of the molecular processes of the normal heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using large-scale single cell and nuclei transcriptomic profiling together with state-of-the-art analytical techniques, we characterise the adult human heart cellular landscape covering six anatomical cardiac regions (left and right atria and ventricles, apex and interventricular septum). Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, revealing distinct subsets in the atria and ventricles indicative of diverse developmental origins and specialized properties. Further we define the complexity of the cardiac vascular network which includes clusters of arterial, capillary, venous, lymphatic endothelial cells and an atrial-enriched population. By comparing cardiac cells to skeletal muscle and kidney, we identify cardiac tissue resident macrophage subsets with transcriptional signatures indicative of both inflammatory and reparative phenotypes. Further, inference of cell-cell interactions highlight a macrophage-fibroblast-cardiomyocyte network that differs between atria and ventricles, and compared to skeletal muscle. We expect this reference human cardiac cell atlas to advance mechanistic studies of heart homeostasis and disease.

show abstract

Population and Single-Cell Analysis of Human Cardiogenesis Reveals Unique LGR5 Ventricular Progenitors in Embryonic Outflow Tract

Abstract: Highlights d Comprehensive gene expression profiles on human cardiogenesis are reported d LGR5 is identified as a key regulator on human-specific conoventriculogenesis d LGR5 signaling may be associated with certain human congenital heart diseases

Cited by 79 publications

References 49 publications

Small-protein Enrichment Assay Enables the Rapid, Unbiased Analysis of Over 100 Low Abundance Factors from Human Plasma

Small-protein Enrichment Assay Enables the Rapid, Unbiased Analysis of Over 100 Low Abundance Factors from Human Plasma

Amnion signals are essential for mesoderm formation in primates

Cells and gene expression programs in the adult human heart

Contact Info

Product

Resources

About