小柯机器人

美国杜克大学医学院Purushothama Rao Tata和Aleksandra Tata共同合作，近期取得重要工作进展。他们研究提出，过渡细胞状态在肺再生过程中塑造组织拓扑结构。相关研究成果2023年11月2日在线发表于《细胞—干细胞》杂志上。

据介绍，器官再生需要动态的细胞相互作用来重建细胞数量和组织结构。虽然研究人员知道替代丢失组织祖细胞的身份，但它们产生的瞬态及其在修复中的作用仍然难以捉摸。

使用多种损伤模型，研究人员发现肺泡成纤维细胞获得以Sfrp1和Runx1为标志的不同状态，这些状态影响组织重塑和重组。出乎意料的是，仅切除肺泡上皮1型（AT1）细胞就足以诱导组织重塑和过渡状态。整合scRNA-seq后显示，RUNX1是成纤维细胞状态的关键驱动因素。重要的是，上皮过渡状态的异位诱导或积聚诱导短暂肺泡成纤维细胞的快速形成，导致器官范围的纤维化。相反，上皮或成纤维细胞过渡状态或RUNX1缺失的消除，导致类似肺气肿的组织简化。

总之，这项工作揭示了过渡状态在再生过程中组织拓扑结构的协调中的关键作用。

附：英文原文

Title: Transitional cell states sculpt tissue topology during lung regeneration

Author: Arvind Konkimalla, Satoshi Konishi, Lauren Macadlo, Yoshihiko Kobayashi, Zachary J. Farino, Naoya Miyashita, Léa El Haddad, Jeremy Morowitz, Christina E. Barkauskas, Pankaj Agarwal, Tomokazu Souma, Mai K. ElMallah, Aleksandra Tata, Purushothama Rao Tata

Issue&Volume: 2023/11/02

Abstract: Organ regeneration requires dynamic cell interactions to reestablish cell numbersand tissue architecture. While we know the identity of progenitor cells that replacelost tissue, the transient states they give rise to and their role in repair remainelusive. Here, using multiple injury models, we find that alveolar fibroblasts acquiredistinct states marked by Sfrp1 and Runx1 that influence tissue remodeling and reorganization. Unexpectedly, ablation of alveolarepithelial type-1 (AT1) cells alone is sufficient to induce tissue remodeling andtransitional states. Integrated scRNA-seq followed by genetic interrogation revealsRUNX1 is a key driver of fibroblast states. Importantly, the ectopic induction oraccumulation of epithelial transitional states induce rapid formation of transientalveolar fibroblasts, leading to organ-wide fibrosis. Conversely, the eliminationof epithelial or fibroblast transitional states or RUNX1 loss, leads to tissue simplificationresembling emphysema. This work uncovered a key role for transitional states in orchestratingtissue topologies during regeneration.

DOI: 10.1016/j.stem.2023.10.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00363-6

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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