이유라 (연세대학교 의과대학)

한빛사논문

조회242

연세대학교 의과대학

J. Am. Soc. Nephrol., Aug 09 2024, | https://doi.org/10.1681/ASN.0000000000000462 Regenerative Role of Lrig1+ Cells in Kidney Repair

Lee, Yura^1,*; Kim, Kwang H.^1,*; Park, Jihwan^2,*; Kang, Hyun Mi³; Kim, Sung-Hee¹; Jeong, Haengdueng¹; Lee, Buhyun¹; Lee, Nakyum¹; Cho, Yejin¹; Kim, Gyeong Dae²; Yu, Seyoung⁴; Gee, Heon Yung⁴; Bok, Jinwoong⁵; Hamilton, Maxwell S.⁶; Gewin, Leslie^7,8; Aronow, Bruce J¹⁰; Lim, Kyung-Min^9,§; Coffey, Robert J.^6,8,§,#; Nam, Ki Taek^1,§,#

¹Department of Biomedical Sciences, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea

²School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea

³Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea

⁴Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea

⁵Department of Anatomy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea

⁶Epithelial Biology Center and Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

⁷Division of Nephrology and Hypertension, Department of Medicine and Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

⁸Department of Medicine, Veterans Affairs Hospital, Tennessee Valley Healthcare System, Nashville, TN 37212, USA

⁹College of Pharmacy, Ewha Womans University, Seoul 03760, Korea

¹⁰Departments of Biomedical Informatics, Developmental Biology, and Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45267, USA

^#Address correspondence to: Dr. Ki Taek Nam, DVM, PhD, Dr. Robert J. Coffey, M.D.

^*These authors share co-first authorship

^§These authors share co-senior authorship.

Abstract

In response to severe kidney injury, the kidney epithelium displays remarkable regenerative capabilities driven by adaptable resident epithelial cells. To date, it has been widely considered that the adult kidney lacks multipotent stem cells; thus, the cellular lineages responsible for repairing proximal tubule damage are incompletely understood. Leucine-rich repeats and immunoglobulin-like domains protein 1-expressing cells (Lrig1+ cells) have been identified as a long-lived cell in various tissues that can induce epithelial tissue repair. Therefore, we hypothesized that Lrig1+ cells participate in kidney development and tissue regeneration. We investigated the role of Lrig1+ cells in kidney injury using mouse models. The localization of Lrig1+ cells in the kidney was examined throughout mouse development. The function of Lrig1+ progeny cells in acute kidney injury repair was examined in vivo using a tamoxifen-inducible Lrig1-specific Cre recombinase-based lineage tracing in three different kidney injury mouse models. Additionally, we conducted single-cell RNA-sequencing to characterize the transcriptional signature of Lrig1+ cells and to trace their progeny. Lrig1+ cells were present during kidney development and contributed to formation of the proximal tubule and collecting duct structures in mature mouse kidneys. In three-dimensional culture, single Lrig1+ cells demonstrated long-lasting propagation and differentiated into the proximal tubule and collecting duct lineages. These Lrig1+ proximal tubule cells highly expressed progenitor-like and quiescence-related genes, giving rise to a novel cluster of cells with regenerative potential in adult kidneys. Moreover, these long-lived Lrig1+ cells expanded and repaired damaged proximal tubules in response to three types of acute kidney injury in mice. These findings highlight the critical role of Lrig1+ cells in kidney regeneration.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-13)
연구진국내(교신)+국외 연구진
분야 의약학 > 응용의학

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