이소민 (서울대학교, Massachusetts General Hospital and Harvard Medical School)

한빛사논문

조회948

서울대학교, Massachusetts General Hospital and Harvard Medical School

CV File 464 kb

Nat. Commun., Jan 03 2024, 15 (1) | https://doi.org/10.1038/s41467-023-44427-0 Angiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts

Somin Lee ^{# 1 2 3}, Hyunkyung Kim^{# 4 5}, Bum Suk Kim ^{# 6}, Sehyun Chae^{# 7}, Sangmin Jung ^{# 8}, Jung Seub Lee ⁸, James Yu ¹, Kyungmin Son ⁸, Minhwan Chung ⁸, Jong Kyoung Kim ^{9 10 *}, Daehee Hwang ^{11 *}, Sung Hee Baek ¹^{2 *}, Noo Li Jeon ^{13 14 15 16 *}

¹Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, South Korea.

²Institute of Advanced Machines and Design, Seoul National University, Seoul, South Korea.

³Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

⁴Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea.

⁵BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, South Korea.

⁶Department of New Biology, DGIST, Daegu, South Korea.

⁷Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu, South Korea.

⁸Department of Mechanical Engineering, Seoul National University, Seoul, South Korea.

⁹Department of New Biology, DGIST, Daegu, South Korea.

¹⁰Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, South Korea.

¹¹School of Biological Sciences, Seoul National University, Seoul, South Korea.

¹²Creative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, Seoul, South Korea.

¹³Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, South Korea.

¹⁴Institute of Advanced Machines and Design, Seoul National University, Seoul, South Korea.

¹⁵Department of Mechanical Engineering, Seoul National University, Seoul, South Korea.

¹⁶Qureator, Inc., San Diego, CA, USA.

^#Contributed equally
^*Corresponding authors: correspondence to Jong Kyoung Kim, Daehee Hwang, Sung Hee Baek or Noo Li Jeon

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.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-05)
연구진국내(교신)+국외 연구진
분야 생명과학 > 세포생물학

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