Tissue-specific endothelial cell heterogeneity in human type 2 diabetes

Bruns, A.-F.; Brown, O. I.; Viswambharan, H.; Witte, K. K.; Straw, S.; Gierula, J.; Cheng, C. W.; Bridge, K.; Haywood, N.; Skromma, A.; Makava, N.; Daly, L. F.; Bourn, M.; Rivera, J. F.; Almuhiim, N.; Drozd, M.; Beech, D. J.; Roberts, L. D.; Naseem, K.; Cubbon, R. M.; Kearney, M. T.

doi:10.64898/2025.12.01.691646

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bioRxiv · 10.64898/2025.12.01.691646

Tissue-specific endothelial cell heterogeneity in human type 2 diabetes

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Abstract

Transcriptomic heterogeneity of microvascular endothelial cells (MVEC) within subcutaneous adipose tissue (SAT) in preclinical models of obesity/type 2 diabetes mellitus (T2DM) is well-established. Here, we examined if such heterogeneity exists between two canonical insulin-target tissues, SAT and skeletal muscle (SkM). Characterisation of SAT and SkM MVEC from humans with T2DM demonstrated that SAT, but not SkM, exhibited cellular stress at transcriptomic, morphological, and protein levels.

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Bruns, A.-F., Brown, O. I., Viswambharan, H., Witte, K. K., Straw, S., Gierula, J., Cheng, C. W., Bridge, K., Haywood, N., Skromma, A., Makava, N., Daly, L. F., Bourn, M., Rivera, J. F., Almuhiim, N., Drozd, M., Beech, D. J., Roberts, L. D., Naseem, K., Cubbon, R. M., Kearney, M. T.. 2025-12-03. Tissue-specific endothelial cell heterogeneity in human type 2 diabetes. https://doi.org/10.64898/2025.12.01.691646

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