小柯机器人

美国杜克大学医学院细胞生物学系Purushothama Rao Tata研究组，利用人类远端肺图和谱系层次揭示了一个双能祖细胞。相关论文于2022年3月30日发表在《自然》杂志上。

使用空间转录组学和微解剖远端气道的单细胞分析，他们确定了分子上不同的末端和呼吸细支气管 (TRB)细胞类型，这些细胞类型以前没有被表征过。这些包括气道相关的 LGR5+ 成纤维细胞和 TRB 特异性肺泡 0 型 (AT0) 细胞和 TRB 分泌细胞 (TRB-SCs)。连接组图和基于类器官的共培养表明 LGR5+ 成纤维细胞在气道生态位中形成了一个信号枢纽。AT0 细胞和 TRB-SCs 在灵长类动物中是保守的，并在人类肺发育过程中动态出现。

使用非人类灵长类动物肺损伤模型，连同人类类器官和组织标本，他们表明再生肺中的肺泡 2 型细胞瞬时获得 AT0 状态，它们可以从中分化成肺泡 1 型细胞或 TRB- SC。这种分化程序不同于在小鼠肺中确定的分化程序。他们的研究还揭示了驱动双能 AT0 细胞状态分化为正常或病理状态的机制。总之，他们的研究结果修正了人类肺细胞图谱和谱系轨迹，并暗示了灵长类动物肺再生和疾病中的上皮过渡状态。

据悉，绘制组成细胞的空间分布和分子特征对于了解健康和疾病中的组织动力学至关重要。研究人员缺乏人类远端气道的综合地图，包括与呼吸系统疾病有关的TRB。

附：英文原文

Title: Human distal lung maps and lineage hierarchies reveal a bipotent progenitor

Author: Kadur Lakshminarasimha Murthy, Preetish, Sontake, Vishwaraj, Tata, Aleksandra, Kobayashi, Yoshihiko, Macadlo, Lauren, Okuda, Kenichi, Conchola, Ansley S., Nakano, Satoko, Gregory, Simon, Miller, Lisa A., Spence, Jason R., Engelhardt, John F., Boucher, Richard C., Rock, Jason R., Randell, Scott H., Tata, Purushothama Rao

Issue&Volume: 2022-03-30

Abstract: Mapping the spatial distribution and molecular identity of constituent cells is essential for understanding tissue dynamics in health and disease. We lack a comprehensive map of human distal airways, including the terminal and respiratory bronchioles (TRBs), which are implicated in respiratory diseases1,2,3,4. Here, using spatial transcriptomics and single-cell profiling of microdissected distal airways, we identify molecularly distinct TRB cell types that have not—to our knowledge—been previously characterized. These include airway-associated LGR5+ fibroblasts and TRB-specific alveolar type-0 (AT0) cells and TRB secretory cells (TRB-SCs). Connectome maps and organoid-based co-cultures reveal that LGR5+ fibroblasts form a signalling hub in the airway niche. AT0 cells and TRB-SCs are conserved in primates and emerge dynamically during human lung development. Using a non-human primate model of lung injury, together with human organoids and tissue specimens, we show that alveolar type-2 cells in regenerating lungs transiently acquire an AT0 state from which they can differentiate into either alveolar type-1 cells or TRB-SCs. This differentiation programme is distinct from that identified in the mouse lung5,6,7. Our study also reveals mechanisms that drive the differentiation of the bipotent AT0 cell state into normal or pathological states. In sum, our findings revise human lung cell maps and lineage trajectories, and implicate an epithelial transitional state in primate lung regeneration and disease.

DOI: 10.1038/s41586-022-04541-3

Source: https://www.nature.com/articles/s41586-022-04541-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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