Cell of origin alters myeloid immunoreactive states in the lung adenocarcinoma microenvironment

Description

The study aims to investigate how the cellular origin of lung adenocarcinoma (LUAD), specifically whether it arises from alveolar type I (AT1) or alveolar type II (AT2) cells, influences the tumor immune microenvironment (TIME), immune cell composition, and metastatic potential. The hypothesis is that AT1- and AT2-derived LUADs exhibit distinct immune landscapes and functional pathways, impacting tumor progression and therapeutic response. Data Description Supplemental File 1: Myeloid_Annotated.RDS (and .zip) Description: Annotated single-nucleus RNA sequencing (snRNA-seq) data focused on myeloid cells from AT1- and AT2-derived LUAD samples. Supplemental File 2: R code for snRNA-seq analyses (R file and .zip) Description: R scripts for preprocessing, clustering, and differential expression analysis of snRNA-seq data. Supplemental File 3: Trajectory analysis (ipynb and .zip) Description: Jupyter notebooks for trajectory inference to trace cell differentiation paths and lineage relationships. Supplemental Files 4-5: CCCObj_in_AT1LUAD.RDS/.zip and CCCObj_in_AT2LUAD.RDS/.zip Description: Cell-cell communication (CCC) analysis objects for AT1- and AT2-derived LUAD, respectively. Supplemental File 6: CCC_analysis via LIANA.Rmd and .zip Description: LIANA analysis scripts for cell-cell communication using snRNA-seq data. Supplemental File 7: STSeq_LUAD_xzcompressed.Rds Description: Spatial transcriptomics (ST) data for LUAD samples, capturing gene expression with spatial context. Supplemental File 8: TIME Visium Analysis (R file and .zip) Description: R scripts for Visium spatial transcriptomics analysis, including data normalization and spatial clustering. Supplemental Tables Supplemental Table 1: Overall Cell Composition (.pdf and .xlsx) Description: Quantitative breakdown of overall cell populations within LUAD samples. Supplemental Table 2: Myeloid Cell Composition (.pdf and .xlsx) Description: Detailed cell-type composition focusing specifically on myeloid populations. Supplemental Table 3: Myeloid Cell Composition per Mouse ID (.pdf and .xlsx) Description: Myeloid cell counts stratified by individual mouse IDs, providing insights into sample variability. Supplemental Table 4: FDR-Corrected MP DEGs_AT1 vs. AT2 (.pdf) Description: Differentially expressed genes (DEGs) between AT1- and AT2-derived LUAD, corrected for false discovery rate (FDR). Supplemental Table 5: PANTHER Pathways for MP DEGs_AT1 vs. AT2 (.pdf and .xlsx) Description: Pathway analysis results for DEGs, highlighting enriched biological processes and signaling pathways. Notable Findings and Key Insights AT1-derived LUAD exhibits a more immunoreactive TIME, with increased T cell infiltration and reduced immunosuppressive MDSCs, compared to AT2-derived LUAD. Spatial transcriptomics reveals distinct localization patterns of immune cells, suggesting differential immune cell recruitment based on tumor cell origin.

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