Angiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts

Somin Lee, Hyunkyung Kim, Bum Suk Kim, Sehyun Chae, Sangmin Jung, Jung Seub Lee, James Yu, Kyungmin Son, Minhwan Chung, Jong Kyoung Kim (), Daehee Hwang (), Sung Hee Baek () and Noo Li Jeon ()
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Somin Lee: Seoul National University
Hyunkyung Kim: Korea University College of Medicine
Bum Suk Kim: DGIST
Sehyun Chae: Korea Brain Research Institute
Sangmin Jung: Seoul National University
Jung Seub Lee: Seoul National University
James Yu: Seoul National University
Kyungmin Son: Seoul National University
Minhwan Chung: Seoul National University
Jong Kyoung Kim: DGIST
Daehee Hwang: Seoul National University
Sung Hee Baek: Seoul National University
Noo Li Jeon: Seoul National University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Several functions of autophagy associated with proliferation, differentiation, and migration of endothelial cells have been reported. Due to lack of models recapitulating angiogenic sprouting, functional heterogeneity of autophagy in endothelial cells along angiogenic sprouts remains elusive. Here, we apply an angiogenesis-on-a-chip to reconstruct 3D sprouts with clear endpoints. We perform single-cell RNA sequencing of sprouting endothelial cells from our chip to reveal high activation of autophagy in two endothelial cell populations- proliferating endothelial cells in sprout basements and stalk-like endothelial cells near sprout endpoints- and further the reciprocal expression pattern of autophagy-related genes between stalk- and tip-like endothelial cells near sprout endpoints, implying an association of autophagy with tip-stalk cell specification. Our results suggest a model describing spatially differential roles of autophagy: quality control of proliferating endothelial cells in sprout basements for sprout elongation and tip-stalk cell specification near sprout endpoints, which may change strategies for developing autophagy-based anti-angiogenic therapeutics.

Date: 2024
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DOI: 10.1038/s41467-023-44427-0

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