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

Autor: Lee S; Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, South Korea.; Institute of Advanced Machines and Design, Seoul National University, Seoul, South Korea.; Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Kim H; Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea.; BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, South Korea., Kim BS; Department of New Biology, DGIST, Daegu, South Korea., Chae S; Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu, South Korea., Jung S; Department of Mechanical Engineering, Seoul National University, Seoul, South Korea., Lee JS; Department of Mechanical Engineering, Seoul National University, Seoul, South Korea., Yu J; Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, South Korea., Son K; Department of Mechanical Engineering, Seoul National University, Seoul, South Korea., Chung M; Department of Mechanical Engineering, Seoul National University, Seoul, South Korea., Kim JK; Department of New Biology, DGIST, Daegu, South Korea. blkimjk@postech.ac.kr.; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, South Korea. blkimjk@postech.ac.kr., Hwang D; School of Biological Sciences, Seoul National University, Seoul, South Korea. daehee@snu.ac.kr., Baek SH; Creative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, Seoul, South Korea. sbaek@snu.ac.kr., Jeon NL; Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, South Korea. njeon@snu.ac.kr.; Institute of Advanced Machines and Design, Seoul National University, Seoul, South Korea. njeon@snu.ac.kr.; Department of Mechanical Engineering, Seoul National University, Seoul, South Korea. njeon@snu.ac.kr.; Qureator, Inc., San Diego, CA, USA. njeon@snu.ac.kr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jan 03; Vol. 15 (1), pp. 230. Date of Electronic Publication: 2024 Jan 03.
DOI: 10.1038/s41467-023-44427-0
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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