Code for letter "The Heterogeneity, Parallel and Divergence of Alveolar Macrophages in Humans and Mice"
The description of rationale and approach included here is duplicated from our publication, in American Journal of Respiratory Cell and Molecular Biology, 2024.
Alveolar macrophages (AMs) maintain airspace homeostasis by clearing excess surfactant, pathogens, and cellular debris. Single-cell RNA sequencing (scRNA-seq) in healthy humans has revealed the heterogeneity of human AMs, identifying subsets with distinct functional gene patterns, such as metal ion binding (MT.AMs), interferon response (IFN.AMs), growth factor secretion, cholesterol and lipid biosynthesis, antigen presentation, and unique chemokine expressions. In contrast, AMs from naïve pathogen-free mice are traditionally viewed as homogeneous. However, in this letter, we demonstrate that mouse AMs exhibit diverse transcriptional profiles similar to their human counterparts. Gene expression profiling revealed several analogous AM subsets in mice, such as IFN.AMs and MT.AMs, alongside with some unique subsets without clear human counterparts. These findings suggest a complex and conserved division of labor in AMs across species. Despite significant parallels, divergences in the subsets of human and mouse AMs arise from different homologous pairs, regulatory networks, and potential exposures. Overall, this letter provides new insights into the transcriptional landscape of AMs, emphasizing their heterogeneity and the evolutionary conservation of their functions.