The Proposed Bone Post-Arterial Type R Capillaries Resolve into Venous and Fatty Acid-Handling Endothelial Cells

Authors

Jain, S., Joseph, J. D., Liu, H., Bhowmick, N. R., Yang, Y., Mundapat, S. N., Machan, R., Glaviano, A., Chandra, A., Dalan, R., Chen, J., Verma, N. K., Cohen-Solal, M., Risbud, M. V., Bozec, A., Kusumbe, A. P.

Abstract

Endothelial specialization is increasingly recognized as a fundamental regulator of tissue homeostasis, yet the cellular diversity of the skeletal vasculature remains incompletely resolved. Here, we integrate large-scale single-cell transcriptomics, cross-tissue comparisons, and imaging to comprehensively define endothelial heterogeneity across the skeleton. Our analyses demonstrate that the proposed post-arterial "type R" endothelial population is not a distinct endothelial subtype but instead comprises canonical venous endothelial cells and fatty acid-handling endothelial state. RNA velocity supports a venous continuum, while the proposed type R markers FMO2, and AQP7 lack both endothelial and skeletal specificity. The fatty acid-handling endothelial state, characterized by Lpl and Cd36 is conserved across multiple skeletal sites and non-skeletal tissues, indicating a general endothelial metabolic programme. Within bone, this endothelial state expands following high-fat diet and is suppressed during injury. Together, these findings redefine skeletal endothelial heterogeneity and establish the proposed type R population as part of a venous continuum.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 29 Jul 2026.

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