성제경 (서울대학교 수의과대학)

한빛사논문

조회659

서울대학교 수의과대학

CV File 112 kb

EBioMedicine, 2023 Dec 19:99:104932 | https://doi.org/10.1016/j.ebiom.2023.104932 A longitudinal molecular and cellular lung atlas of lethal SARS-CoV-2 infection in K18-hACE2 transgenic mice

Seunghoon Choi ^a,b,s, Jusung Lee ^c,s, Suhyeon Kim ^b,d,s, Youn Woo Lee ^e,s, Gi-Cheon Kim ^j,k, Seung-Min Hong ^f, Se-Hee An ^f, Hyuna Noh ^b, Kyung Eun Kim ^a,b, Dain On ^a,b, Sang Gyu Lee ^b,g, Hui Jeong Jang^e, Sung-Hee Kim ^h,i, Jiseon Kim ^h,i, Jung Seon Seo ^h,i, Jeong Jin Kim ^h,i, In Ho Park ^h,j, Jooyeon Oh ^i,j,k, Da-Jung Kim^i,j,k, Jong-Hwi Yoon ^j,k, Sang-Hyuk Seok ^l, Yu Jin Lee ^l, Seo Yeon Kim ^m, Young Been Kim^m, Ji-Yeon Hwang ^m, Hyo-Jung Lee ⁿ, Hong Bin Kim ^o, Jun Won Park ^l, Jun-Won Yun ^p, Jeon-Soo Shin ^h,i,j,k, Jun-Young Seo ^h,i, Ki Taek Nam ^h,i, Kang-Seuk Choi ^f, Ho-Keun Kwon ^i,j,k, Ho-Young Lee ^e,q, Jong Kyoung Kim ^c,r, Je Kyung Seong ^a,b,d,g

^aLaboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK21 Project for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea

^bKorea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Republic of Korea

^cDepartment of New Biology, DGIST, Daegu 42988, Republic of Korea

^dBIO-MAX Institute, Seoul National University, Seoul 08826, Republic of Korea

^eDepartment of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam 23488, Republic of Korea

^fLaboratory of Avian Diseases, BK21 Project for Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea

^gInterdisciplinary Program for Bioinformatics, Seoul National University, Seoul 08826, Republic of Korea

^hDepartment of Biomedical Sciences, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

ⁱGraduate School of Medical Science, BK21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

^jInstitute of Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

^kDepartment of Microbiology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

^lDivision of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24342, Republic of Korea

^mPreclinical Research Center, Seoul National University Bundang Hospital, Seongnam 23488, Republic of Korea

ⁿDepartment of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital, Seongnam 23620, Republic of Korea

^oDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 23620, Republic of Korea

^pLaboratory of Veterinary Toxicology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Republic of Korea

^qDepartment of Nuclear Medicine, Seoul National University, College of Medicine, Seoul 03080, South Korea

^rDepartment of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea

^sEqual first authors.

Corresponding authors : Kang-Seuk Choi, Ho-Keun Kwon, Ho-Young Lee, Jong Kyoung Kim, Je Kyung Seong

Abstract

Background: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus's impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research.

Methods: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue.

Findings: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor-ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFβ signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes.

Interpretation: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFβ signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-22)
연구진국내 연구진
분야 생명과학 > 수의학

댓글 작성 로그인

CV 열람하기

연락처 보기