Single-cell transcriptomics of murine mural cells reveals cellular heterogeneity

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ngle-cell transcriptomics of murine mural cells reveals cellular heterogeneity 1†

2†

2*

Ya-Na Guan , Yue Li , Moom Roosan & Qing Jing 1

1*

Shanghai Jiao Tong University School of Medicine (SJTUSM) & CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai 200031, China; 2 Chapman University, Irvine, CA 92618, USA Received July 30, 2020; accepted September 23, 2020; published online November 3, 2020

Mural cells (MCs) wrap around the endothelium, and participate in the development and homeostasis of vasculature. MCs have been reported as heterogeneous population morphologically and functionally. However, the transcriptional heterogeneity of MCs was rarely studied. In this study, we illustrated the transcriptional heterogeneity of MCs with different perspectives by using publicly available single-cell dataset GSE109774. Specifically, MCs are transcriptionally different from other cell types, and ligand-receptor interactions of different cells with MCs vary. Re-clustering of MCs identified five distinct subclusters. The heterogeneity of MCs in tissues was reflected by MC coverage, various distribution of MC subclusters, and ligand-receptor interactions of MCs and parenchymal cells. The transcriptomic diversity of MCs revealed in this article will help facilitate further research into MCs. mural cells, single-cell analysis, heterogeneity Citation:

Guan, Y.N., Li, Y., Roosan, M., and Jing, Q. (2020). Single-cell transcriptomics of murine mural cells reveals cellular heterogeneity. Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1823-2

INTRODUCTION Mural cells (MCs), which support the structure of vessels and play vital roles in maintaining vascular homeostasis (Armulik et al., 2011), mainly consist of vascular smooth muscle cells (VSMCs) and pericytes (PCs) in vasculature. MCs are ubiquitously distributed along the abluminal endothelium and the phenotype varies with the hierarchically distributed microvascular tree, which contains arterioles, precapillary arterioles, capillaries, postcapillary venules, and venules (Hartmann et al., 2015). Specifically, PCs extend along the capillary bed with nearly rounded cell bodies and their derived cytoplasmic processes (Armulik et al., 2005; Borysova et al., 2013). VSMCs cover larger blood vessels †Contributed equally to this work *Corresponding authors (Moom Roosan, email: [email protected]; Qing Jing, email: [email protected])

with different morphology (Rensen et al., 2007). Generally, arteriolar endothelium-encircled VSMCs are spindle-shaped, tightly arranged cells without cytoplasmic process. By contrast, VSMCs along the venules are bigger, stellate-shaped, with many slender, branching cytoplasmic processes. The phenotype of mural cells in precapillary arterioles and postcapillary venules gradually transits from VSMCs to PCs and vice versa. The diversity of mural cells extends beyond the phenotypes mentioned above. In fact, the ultrastructure and function of MCs in different