Journal: bioRxiv
Article Title: Functional interrogation uncovers a critical role for a high-plasticity cell state in lung adenocarcinoma
doi: 10.1101/2025.10.03.680232
Figure Lengend Snippet: a, Heatmap of Pearson correlations calculated between the HPCS and recurrent pan-cancer cell states (AC: astrocyte-like cell state, OPC: oligodendrocyte progenitor cell-like, NPC: neural progenitor cell-like) , divided by cancer type (BC: breast cancer, CRC: colorectal cancer, HNC: head and neck cancer, LUAD: lung adenocarcinoma, OC: ovarian cancer, PCa: prostate adenocarcinoma, PDAC: pancreatic ductal adenocarcinoma, SCC: squamous cell carcinoma of the skin, ALL: acute lymphoblastic leukemia, MM: multiple myeloma). Arrow indicates the Stress -associated cell state from ref. . A full list of studies is listed in Supplementary Table 5 . b, Pearson correlation between the HPCS signature score ( x -axis) and plastic cell states ( y -axis) from either colorectal cancer (OF/HRC: oncofetal/core high relapse , ) ( top ), and pancreatic ductal adenocarcinoma (scBasal ) ( middle ), or castration-resistant prostate cancer adenocarcinoma (Plasticity ) ( bottom ). Two-tailed p value calculated from the exact distribution of Pearson correlation coefficient. c , Heatmaps demonstrating mean gene signature score in either SLC4A11 or PLAUR negative and positive cells scaled using a z-score generated per program to compare gene signatures across different cancer types in human scRNA-seq datasets ( Supplementary Table 5 ). For each dataset gene pair, significance is calculated by comparing positive vs negative cells and depicted in the positive cell column. Four human LUAD datasets are shown [LungM 5 ; LungK ; LungB ; LungD ] along with plastic cell states [OF/HRC , , lowerSpike , Plasticity ] in other cancers [CRC ; SCC ; PCa ; PDAC ; HNC_C , HNC_K , OC ]. t-test. d, Immunofluorescence of human LUAD stained for (top) uPAR (green) and integrin α2 (red) or (bottom) pan-cytokeratin (white). Arrows point to uPAR and integrin α2 double positive cells. Scale bar: 25 μm. e, Heatmaps demonstrating mean gene signature score in either Slc4a11 or Plaur negative and positive cells scaled using a z-score generated per program to compare gene signatures across different injury models in mouse single cell datasets ( Supplementary Table 5 ). Heatmaps of signature scores represented as z-scores of the indicated regenerative programs in Lung (DATP: damage associated transient progenitor ; ADI: KRT8 + alveolar differentiation intermediate ; PATS: pre-alveolar type-1 transitional cell state ), Pancreas (scBasal cell state ), Intestine (revSC: revival stem cell ; SSC2: singly profiled stem cell cluster 2 ) and Skin (Wound ). For each dataset gene pair, significance is calculated by comparing positive vs negative cells and depicted in the positive cell column. t-test. f, Representative multiplex FISH staining of Slc4a11 (red) and Sftpc (green) in normal lungs vs. 7 days following hyperoxia-induced lung injury. Scale bar: 10 µm.
Article Snippet: Alveolar injury was induced in young C57BL/6 mice by a 32 hour exposure to >85% O 2 in a hyperoxia chamber (BioSpherix), with FiO 2 concentration maintained at a constant flow of ∼3 L O 2 /minute and monitored by an in-line oxygen analyzer.
Techniques: Two Tailed Test, Generated, Immunofluorescence, Staining, Multiplex Assay
![a, Heatmap of Pearson correlations calculated between the HPCS and recurrent pan-cancer cell states (AC: astrocyte-like cell state, OPC: oligodendrocyte progenitor cell-like, NPC: neural progenitor cell-like) , divided by cancer type (BC: breast cancer, CRC: colorectal cancer, HNC: head and neck cancer, LUAD: lung adenocarcinoma, OC: ovarian cancer, PCa: prostate adenocarcinoma, PDAC: pancreatic ductal adenocarcinoma, SCC: squamous cell carcinoma of the skin, ALL: acute lymphoblastic leukemia, MM: multiple myeloma). Arrow indicates the Stress -associated cell state from ref. . A full list of studies is listed in Supplementary Table 5 . b, Pearson correlation between the HPCS signature score ( x -axis) and plastic cell states ( y -axis) from either colorectal cancer (OF/HRC: oncofetal/core high relapse , ) ( top ), and pancreatic ductal adenocarcinoma (scBasal ) ( middle ), or castration-resistant prostate cancer adenocarcinoma (Plasticity ) ( bottom ). Two-tailed p value calculated from the exact distribution of Pearson correlation coefficient. c , Heatmaps demonstrating mean gene signature score in either SLC4A11 or PLAUR negative and positive cells scaled using a z-score generated per program to compare gene signatures across different cancer types in human scRNA-seq datasets ( Supplementary Table 5 ). For each dataset gene pair, significance is calculated by comparing positive vs negative cells and depicted in the positive cell column. Four human LUAD datasets are shown [LungM 5 ; LungK ; LungB ; LungD ] along with plastic cell states [OF/HRC , , lowerSpike , Plasticity ] in other cancers [CRC ; SCC ; PCa ; PDAC ; HNC_C , HNC_K , OC ]. t-test. d, Immunofluorescence of human LUAD stained for (top) uPAR (green) and integrin α2 (red) or (bottom) pan-cytokeratin (white). Arrows point to uPAR and integrin α2 double positive cells. Scale bar: 25 μm. e, Heatmaps demonstrating mean gene signature score in either Slc4a11 or Plaur negative and positive cells scaled using a z-score generated per program to compare gene signatures across different injury models in mouse single cell datasets ( Supplementary Table 5 ). Heatmaps of signature scores represented as z-scores of the indicated regenerative programs in Lung (DATP: damage associated transient progenitor ; ADI: KRT8 + alveolar differentiation intermediate ; PATS: pre-alveolar type-1 transitional cell state ), Pancreas (scBasal cell state ), Intestine (revSC: revival stem cell ; SSC2: singly profiled stem cell cluster 2 ) and Skin (Wound ). For each dataset gene pair, significance is calculated by comparing positive vs negative cells and depicted in the positive cell column. t-test. f, Representative multiplex FISH staining of Slc4a11 (red) and Sftpc (green) in normal lungs vs. 7 days following <t>hyperoxia-induced</t> lung injury. Scale bar: 10 µm.](https://bio-rxiv-images-cdn.bioz.com/dois_ending_with_32/10__1101_slash_2025__10__03__680232/10__1101_slash_2025__10__03__680232___F5.large.jpg)