美国加州大学洛杉矶分校戴维·格芬医学院Brigitte N. Gomperts和Manash K. Paul研究团队合作发现，不同时空动态分泌Wnt的生态位调节近端气道再生和衰老。这一研究成果于2020年7月27日发表在《细胞-干细胞》上。

他们利用转基因小鼠和药理研究，发现气道基底干细胞（ABSCs）中的Wnt /β-catenin对于体内损伤后的增殖至关重要。ABSC来源的Wnt配体的产生对于上皮增殖是必不可少的，相反，软骨间带（ICZ）生态位中的PDGFRα+谱系会短暂分泌ABSC增殖所需的Wnt配体。

引人注目的是，ABSC来源的Wnt配体随后促使早期祖细胞分化为纤毛细胞。他们发现了衰老的其他变化，因为源自ABSC的腺样上皮内陷（GLEI）在衰老小鼠的ICZ中排他性地出现，并有助于气道稳态和修复。此外，ABSC Wnt配体分泌对于GLEI的形成，以及β-连环蛋白在年轻小鼠中组成性激活，诱导其在体内的形成所必须的。

总体而言，这些数据强调了多个时空动态的Wnt分泌生态位，这些生态位调节了气道再生和衰老的不同阶段功能。

研究人员表示，我们对ABSC及其稳态、损伤和衰老中信号传导生态位之间动态相互作用的理解仍然不清楚。

附：英文原文

Title: Distinct Spatiotemporally Dynamic Wnt-Secreting Niches Regulate Proximal Airway Regeneration and Aging

Author: Cody J. Aros, Preethi Vijayaraj, Carla J. Pantoja, Bharti Bisht, Luisa K. Meneses, Jenna M. Sandlin, Jonathan A. Tse, Michelle W. Chen, Arunima Purkayastha, David W. Shia, Jennifer M.S. Sucre, Tammy M. Rickabaugh, Eszter K. Vladar, Manash K. Paul, Brigitte N. Gomperts

Issue&Volume: 2020-07-27

Abstract: Our understanding of dynamic interactions between airway basal stem cells (ABSCs)and their signaling niches in homeostasis, injury, and aging remains elusive. Usingtransgenic mice and pharmacologic studies, we found that Wnt/β-catenin within ABSCswas essential for proliferation post-injury in vivo. ABSC-derived Wnt ligand production was dispensable for epithelial proliferation.Instead, the PDGFRα+ lineage in the intercartilaginous zone (ICZ) niche transiently secreted Wnt ligandnecessary for ABSC proliferation. Strikingly, ABSC-derived Wnt ligand later droveearly progenitor differentiation to ciliated cells. We discovered additional changesin aging, as glandular-like epithelial invaginations (GLEIs) derived from ABSCs emergedexclusively in the ICZ of aged mice and contributed to airway homeostasis and repair.Further, ABSC Wnt ligand secretion was necessary for GLEI formation, and constitutiveactivation of β-catenin in young mice induced their formation in vivo. Collectively, these data underscore multiple spatiotemporally dynamic Wnt-secretingniches that regulate functionally distinct phases of airway regeneration and aging.

DOI: 10.1016/j.stem.2020.06.019

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30286-1