Publication
Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelium
Publisher:
Springer Science and Business Media LLC
Date:
24-11-2022
DOI:
10.1038/S41467-022-34425-Z
Abstract: Heterogeneity of endothelial cell (EC) populations reflects their erse functions in maintaining tissue’s homeostasis. However, their phenotypic, molecular, and functional properties are not entirely mapped. We use the Tie2-CreERT2 Rosa26-tdTomato reporter mouse to trace, profile, and cultivate primary ECs from different organs. As paradigm platform, we use this strategy to study bone marrow endothelial cells (BMECs). Single-cell mRNA sequencing of primary BMECs reveals that their ersity and native molecular signatures is transitorily preserved in an ex vivo culture that conserves key cell-to-cell microenvironment interactions. Macrophages sustain BMEC cellular ersity and expansion and preserve sinusoidal-like BMECs ex vivo. Endomucin expression discriminates BMECs in populations exhibiting mutually exclusive properties and distinct sinusoidal/arterial and tip/stalk signatures. In contrast to arterial-like, sinusoidal-like BMECs are short-lived, form 2D-networks, contribute to in vivo angiogenesis, and support hematopoietic stem rogenitor cells in vitro. This platform can be extended to other organs’ ECs to decode mechanistic information and explore therapeutics.