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Commentary

12 June 2024

Dual Genetic Tracing Reveals the Origin of Alveolar Stem Cells after Lung Injury

As alveolar epithelial stem cells, alveolar type II (AT2) cells play a pivotal role in sustaining alveolar homeostasis and facilitating repair processes. However, the sources of AT2 cell regeneration have remained contentious due to the non-specific labeling limitations of traditional single recombinase-based lineage tracing techniques. To address this issue, we employed dual recombination systems to develop more precise lineage tracing methodologies, effectively bypassing the shortcomings of conventional approaches and enabling specific labeling of lung epithelial cells. Our findings demonstrate that, following lung injury, regenerated AT2 cells do not originate from alveolar type I (AT1) cells, but instead derive from bronchiolar club cells and bronchioalveolar stem cells (BASCs), alongside the self-renewal of resident AT2 cells. Furthermore, we discovered that the transition of club cells and BASCs into AT2 cells is distinctly modulated by the Notch signaling pathway. This study not only provides novel insights into lung regeneration, but the innovative lineage tracing technology developed herein also holds promise as a technical support for research in diverse fields.

Keywords: Genetic lineage tracing; Lung regeneration; Alveolar stem cell; Cre-loxP; Dre-rox
Kuo Liu   Bin Zhou*  

Perspective

04 March 2024

Trees—Protectors against a Changing Climate

There are estimated to be about 3 trillion trees on Earth, or about half the number that existed before the dawn of human civilization. Trees are vital to at least four major biogeochemical cycles, namely, the carbon, water, nitrogen and oxygen cycles. In addition to absorbing carbon, and releasing oxygen through photosynthesis, trees are critical for maintaining biodiversity, providing habitat for 80% of land based wildlife, feeding the soil, generating clouds and increasing albedo (thus causing global cooling), influencing rainfall and weather patterns. The loss of trees, therefore, weakens our chances of reaching climate and biodiversity targets, and so proforestation and other practices to stringently preserve the functionality of and holistically restore forest ecosystems, must be adopted as a matter of urgency, paying due attention to soil, and species diversity including mycorrhizae; not being limited to insouciant “tree planting” solutions. Indeed, due to the tardiness of our actions to repair the Earth and its climate, severe restrictions to the cutting of mature trees must actually be enabled globally. However, this alone is not enough, and must be integrated with other forms of land, wetland, grassland and agricultural protection and restoration. Such Nature Based Solutions could provide over one-third of the climate mitigation needed by 2030 to keep within the 2 °C global heating limit. Nonetheless, it is also critical to curb greenhouse gas emissions at source, not only by implementing low-carbon, renewable energy, but also energy demand reduction strategies, such as insulating buildings, societal relocalisation, and local food growing.

Keywords: Proforestation; Deforestation; Climate change; Biodiversity loss; Natural regeneration; Nature based solutions; Overshoot; Behavioural crisis

Article

19 February 2024

Single Cell Analysis of Lung Lymphatic Endothelial Cells and Lymphatic Responses during Influenza Infection

Tissue lymphatic vessels network plays critical roles in immune surveillance and tissue homeostasis in response to pathogen invasion, but how lymphatic system per se is remolded during infection is less understood. Here, we observed that influenza infection induces a significant increase of lymphatic vessel numbers in the lung, accompanied with extensive proliferation of lymphatic endothelial cells (LECs). Single-cell RNA sequencing illustrated the heterogeneity of LECs, identifying a novel PD-L1+ subpopulation that is present during viral infection but not at steady state. Specific deletion of Pd-l1 in LECs elevated the expansion of lymphatic vessel numbers during viral infection. Together these findings elucidate a dramatic expansion of lung lymphatic network in response to viral infection, and reveal a PD-L1+ LEC subpopulation that potentially modulates lymphatic vessel remolding.

Keywords: Lymphatic endothelial cells (LECs); Single cell; Influenza infection; Lung injury; Regeneration; scRNA-seq; PD-L1
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