Fig 2: Loss of Dll-driven Notch signaling results in expansion of the NEBs.(A–B) Ascl1 immunofluorescence (IF) in E14.5 control lungs (A) showing discrete clusters of Ascl1+ NEBs in large intrapulmonary airways (bronchi: br) in contrast to the aberrant NEB expansion in Dll1cnull; Dll4cnull lungs. At E18.5 (B) NEBs at branchpoints are also enlarged in mutants compared to controls and express Cgrp (bottom panel). (C) Double Ki67; Ascl1 IF shows no evidence that NEB expansion results from increased proliferation at E18.5 (top) or E14.5 (bottom panel). (D) qPCR analysis of NE markers at E18.5: significant increase in Ascl1 and Cgrp expression in double null mutants compared to controls; single mutant Dll1cnull but not Dll4cnull showed increased expression of Ascl1 (n = 3 Dll1 control, n = 5 Dll1cnull for Ascl1 and n = 4 Dll1 control, n = 5 Dll1cnull for Cgrp; n = 3 Dll4 control n = 6 Dll4cnull for Ascl1 and Cgrp; n = 3 Dll1/Dll4 control; n = 3 Dll1cnull; Dll4cnull for Ascl1 and Cgrp). Graphs: mean ± SEM. ***p<0.0005; n.s., not significant by Student’s t-test (E) Morphometric analysis of PNECs and NEBs in E14.5 control and Dll mutant lungs. Left panel: NEB size as determined by number of PNECs per NEB. Center panel: solitary PNEC per airway. Right panel: number of NEBs. * P<0.05, ** P<0.005, *** P<0.0005; n.s., not significant by Student’s t-test. Scale bars in A, B = 40 μm.

Fig 3: Akt supports intracellular lipid levels, proliferation and survival of human PAH PAVSMC. (A,B) Human PAH PAVSMC were incubated in serum deprived media supplemented with 0.1% lipid deprived BSA in presence of Akt inhibitor VIII (10 μM) or diluent. Forty-eight hours later neutral lipid accumulation was evaluated by fluorescent BODIPY 493/503 staining (green) followed by DAPI co-staining (blue) to detect nuclei. Representative images (A) and statistical analysis (B) are shown. Bar equals 50 μm. Data are means ± SE, fold to the diluent-treated cells, n = 5 subjects/group, *p < 0.05 by Mann–Whitney U test. (C) Human PAH PAVSMC were serum deprived in media, supplemented with regular 0.1% BSA, and were treated with 1, 5 μM (C) or 10 μM (D) Akt inhibitor VIII or vehicle (0/-) for 48 h followed by proliferation (Ki-67) (C) or apoptosis (D) analyses. Data are percentage of Ki-67- or TUNEL- positive cells/total number of cells, means ± SE, n = 5 subjects/group. *p < 0.05 Kruskal–Wallis rank test with Dunn pairwise comparison post hoc test (C) or by Mann–Whitney U test (D). (E) Schematic representation of the proposed regulation of the de novo lipid synthesis, required for increased proliferation and survival of PAVSMC in PAH.

Fig 4: Macrophage NCOR1 (nuclear receptor corepressor 1) deficiency inhibits proliferation of cardiac macrophages after myocardial infarction. A, Representative immunofluorescence staining of MAC2 and BrdU in peri‐infarct region of hearts from littermate control and macrophage Ncor1 knockout mice 7 days after myocardial infarction. The arrows point to MAC2/BrdU double‐positive cells. Scale bar: 200 µm. B, Quantification of MAC2‐positve cells and MAC2/BrdU double‐positive cells. n=3:3. C, Representative flow cytometry analysis of macrophages in whole hearts from littermate control and macrophage Ncor1 knockout mice 7 days after myocardial infarction. D, Quantification of CD11B+F4/80+ macrophages. n=5:4. E, Representative flow cytometry analysis of KI67+ macrophages in whole hearts from littermate control and macrophage Ncor1 knockout mice 7 days after myocardial infarction. F, Quantification of KI67+ macrophages. n=5:4. Values are expressed as mean±SEM. BrdU indicates bromodeoxyuridine; KI67, nuclear proliferation antigen; LC, littermate control; MAC2, galectin3; MNKO, macrophage Ncor1 knockout; and SSC, side scatter. *P<0.05, **P<0.01.

Fig 5: H. pylori induce an IFN-γ response.a Immunofluorescence images of antrum tissue from uninfected (n = 3) and 2-month PMSS1 WT H. pylori-infected (n = 3) mice. Relative abundance of the Muc5ac+, Ki67+, and GSII+ compartments were quantified. b Representative images of H&E staining and gland height quantification of antrum tissue from C57BL/6 mice infected for two months with PMSS1 WT (n = 3) or ΔCagE H. pylori (n = 3). c Immunofluorescence images labeled for Ki67 and quantification of Ki67+ cells per gland in antrum tissue from C57BL/6 mice infected for two months with PMSS1 WT (n = 3) or ΔCagE H. pylori (n = 3). d Sm-ISH for Bmp2 and quantification of Bmp2 signal area per image in antrum tissue from C57BL/6 mice infected for 2 months with PMSS1 WT (n = 3) or ΔCagE H. pylori (n = 3). e GSEA with the hallmark of IFN-γ response genes for PMSS1 WT H. pylori-infected (n = 2) compared to uninfected C57BL/6 mice (n = 2). f qPCR for Ifnγ in the gastric antrum from C57BL/6 mice infected for 2 months with PMSS1 WT (n = 3) or ΔCagE H. pylori (n = 3). g Immunofluorescence images of antrum tissue from 6-week H. pylori-infected C57BL/6 mice (n = 4) and IfnγR KO mice (n = 4). Gland height of antrum tissue and relative abundance of the Muc5ac+, Ki67+, and GSII+ compartments were quantified. h CFUs from 6-week H. pylori-infected C57BL/6 mice (n = 4) and IfnγR KO mice (n = 4). i, j Sm-ISH images and quantification for Bmp2 and Id1 in antrum tissue of 6-week H. pylori-infected C57BL/6 mice (n = 4) and IfnγR KO mice (n = 4). Images are representative of at least three biological replicates. Scale bar: 100 µm, data are presented as mean ± SEM. Statistical analyses were performed using Student’s t-test (two-tailed) for (a–d, f–h, j). Source data are provided as a Source Data file.