이주현 (University of Cambridge) | 한빛사논문 > 한빛사

한빛사논문

조회1,993

University of Cambridge

Cell Stem Cell, Published: August 03, 2020 | DOI:https://doi.org/10.1016/j.stem.2020.06.020 Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration

Jinwook Choi¹, Jong-Eun Park², Georgia Tsagkogeorga^3,4, Motoko Yanagita⁵, Bon-Kyoung Koo⁶, Namshik Han³, Joo-Hyeon Lee^1,7,8,*

¹Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
²Wellcome Sanger Institute, Cambridge, UK
³Milner Therapeutics Institute, University of Cambridge, Cambridge, UK
⁴STORM Therapeutics Ltd., Cambridge, UK
⁵Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
⁶Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna, Austria
⁷Department of Physiology, Development and Neurobiology, University of Cambridge, Cambridge, UK
⁸Lead Contact

^*Corresponding author

Abstract

Tissue regeneration is a multi-step process mediated by diverse cellular hierarchies and states that are also implicated in tissue dysfunction and pathogenesis. Here we leveraged single-cell RNA sequencing in combination with in vivo lineage tracing and organoid models to finely map the trajectories of alveolar-lineage cells during injury repair and lung regeneration. We identified a distinct AT2-lineage population, damage-associated transient progenitors (DATPs), that arises during alveolar regeneration. We found that interstitial macrophage-derived IL-1β primes a subset of AT2 cells expressing Il1r1 for conversion into DATPs via a HIF1α-mediated glycolysis pathway, which is required for mature AT1 cell differentiation. Importantly, chronic inflammation mediated by IL-1β prevents AT1 differentiation, leading to aberrant accumulation of DATPs and impaired alveolar regeneration. Together, this stepwise mapping to cell fate transitions shows how an inflammatory niche controls alveolar regeneration by controlling stem cell fate and behavior.

Keywords : lung stem cells, regeneration, lineage differentiation, inflammation, stem cell niche, IL-1R1 and IL-1β, damage-associated transient progenitors, stem cell fate

논문정보

형식Research article
게재일2020년 08월 (BRIC 등록일 2020-08-07)
연구진국외 연구진
분야 생명과학 > 세포생물학

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