Spatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis

Madhav Mantri, Gaetano J. Scuderi, Roozbeh Abedini-Nassab, Michael F. Z. Wang, David McKellar, Hao Shi, Benjamin Grodner, Jonathan T. Butcher () and Iwijn De Vlaminck ()
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Madhav Mantri: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University
Gaetano J. Scuderi: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University
Roozbeh Abedini-Nassab: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University
Michael F. Z. Wang: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University
David McKellar: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University
Hao Shi: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University
Benjamin Grodner: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University
Jonathan T. Butcher: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University
Iwijn De Vlaminck: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Single-cell RNA sequencing is a powerful tool to study developmental biology but does not preserve spatial information about tissue morphology and cellular interactions. Here, we combine single-cell and spatial transcriptomics with algorithms for data integration to study the development of the chicken heart from the early to late four-chambered heart stage. We create a census of the diverse cellular lineages in developing hearts, their spatial organization, and their interactions during development. Spatial mapping of differentiation transitions in cardiac lineages defines transcriptional differences between epithelial and mesenchymal cells within the epicardial lineage. Using spatially resolved expression analysis, we identify anatomically restricted expression programs, including expression of genes implicated in congenital heart disease. Last, we discover a persistent enrichment of the small, secreted peptide, thymosin beta-4, throughout coronary vascular development. Overall, our study identifies an intricate interplay between cellular differentiation and morphogenesis.

Date: 2021
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DOI: 10.1038/s41467-021-21892-z

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