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

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.

2026-07-28 cell biology
10.64898/2026.07.27.741009 bioRxiv
Show 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.

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