美国剑桥大学Joo-Hyeon Lee研究组取得最新进展。他们发现炎性信号诱导AT2细胞来源的损伤相关瞬时祖细胞来介导肺泡再生。相关论文发表在2020年8月3日出版的《细胞-干细胞》杂志上。

他们利用单细胞RNA测序与体内谱系追踪以及类器官模型相结合，精确绘制了损伤修复和肺再生过程中肺泡谱系细胞的轨迹。他们确定了一个独特的AT2谱系群体，损伤相关的瞬时祖细胞（DATP），其发生在肺泡再生期间。他们发现，间质巨噬细胞来源的IL-1β引发了表达Il1r1的AT2细胞亚群，可通过HIF1α介导的糖酵解途径转化为DATP，这是成熟AT1细胞分化所必需的。

重要的是，由IL-1β介导的慢性炎症会阻止AT1分化，从而导致DATP异常积累并损害肺泡再生。总之，这种逐步映射到细胞命运的转变表明，炎性微环境如何通过控制干细胞的命运和行为来控制肺泡再生。

据介绍，组织再生是由不同的细胞层次和状态介导的多步骤过程，其也与组织功能障碍和发病机理有关。

附：英文原文

Title: Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration

Author: Jinwook Choi, Jong-Eun Park, Georgia Tsagkogeorga, Motoko Yanagita, Bon-Kyoung Koo, Namshik Han, Joo-Hyeon Lee

Issue&Volume: 2020-08-03

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.

DOI: 10.1016/j.stem.2020.06.020

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30287-3