Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelium

Young-Woong Kim (), Greta Zara, HyunJun Kang, Sergio Branciamore, Denis O’Meally, Yuxin Feng, Chia-Yi Kuan, Yingjun Luo, Michael S. Nelson, Alex B. Brummer, Russell Rockne, Zhen Bouman Chen, Yi Zheng, Angelo A. Cardoso and Nadia Carlesso ()
Additional contact information
Young-Woong Kim: Beckman Research Institute, City of Hope
Greta Zara: Beckman Research Institute, City of Hope
HyunJun Kang: Beckman Research Institute, City of Hope
Sergio Branciamore: Beckman Research Institute, City of Hope
Denis O’Meally: Beckman Research Institute, City of Hope
Yuxin Feng: Cincinnati Children’s Hospital Medical Center
Chia-Yi Kuan: University of Virginia School of Medicine
Yingjun Luo: Beckman Research Institute, City of Hope
Michael S. Nelson: Beckman Research Institute, City of Hope
Alex B. Brummer: Beckman Research Institute, City of Hope
Russell Rockne: Beckman Research Institute, City of Hope
Zhen Bouman Chen: Beckman Research Institute, City of Hope
Yi Zheng: Cincinnati Children’s Hospital Medical Center
Angelo A. Cardoso: Beckman Research Institute, City of Hope
Nadia Carlesso: Beckman Research Institute, City of Hope

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Heterogeneity of endothelial cell (EC) populations reflects their diverse 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 diversity and native molecular signatures is transitorily preserved in an ex vivo culture that conserves key cell-to-cell microenvironment interactions. Macrophages sustain BMEC cellular diversity 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/progenitor cells in vitro. This platform can be extended to other organs’ ECs to decode mechanistic information and explore therapeutics.

Date: 2022
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DOI: 10.1038/s41467-022-34425-z

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