Sylven, C. | Search bioRxiv

bioRxiv2022

High cardiomyocyte diversity in human early prenatal heart development

Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Thus, we have characterized human prenatal cardiomyocytes, 6.5- 7 weeks post-conception, in detail by integrating single-cell RNA sequencing, spatial transcriptomics, and ligand-receptor interaction information. Using a computational workflow developed to dissect cell type heterogeneity, localize cell types, and explore their molecular interactions, we identified eight types of developing cardiomyocyte, more than double compared to the ones identified in the Human Developmental Cell Atlas. These have high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles, including outflow tract, and atria, including sinoatrial node. Moreover, cardiomyocyte ligand-receptor crosstalk is mainly with non-cardiomyocyte cell types, encompassing cardiogenesis-related pathways. Thus, early prenatal human cardiomyocytes are highly heterogeneous and develop unique location-dependent properties, with complex ligand-receptor crosstalk. Further elucidation of their developmental dynamics may give rise to new therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/482029v1_ufig1.gif" ALT="Figure 1"> View larger version (76K): org.highwire.dtl.DTLVardef@1385cb8org.highwire.dtl.DTLVardef@14f62d1org.highwire.dtl.DTLVardef@e0b10borg.highwire.dtl.DTLVardef@1876345_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2021

De novo spatiotemporal modelling of cell-type signatures identifies novel cell populations in the developmental human heart

With the emergence of high throughput single cell techniques, the understanding of cellular diversity in biologically complex processes has rapidly increased. The next step towards comprehension of e.g. key organs in the mammal development is to obtain spatiotemporal atlases of the cellular diversity. However, targeted cell typing approaches relying on existing single cell data achieve incomplete and biased maps that could mask the molecular and cellular heterogeneity present in a tissue slide. Here we applied spage2vec, a de novo approach to spatially resolve and characterize cellular diversity during human heart development. We obtained well defined spatial maps of tissue samples from 4.5 to 9 post conception weeks, not biased by probabilistic cell typing approaches. We found previously unreported molecular diversity within cardiomyocytes and epicardial cells and identified their characteristic expression signatures by matching them with specific subpopulations found in single cell RNA sequencing datasets.

developmental biology↗