Skip to main content
. 2022 Dec 5;11:e78216. doi: 10.7554/eLife.78216

Figure 5. Patterns of sensory gene expression in individual PNECs.

(A) Patterns of expression from scRNA-seq profiles of sensory genes (colored dots, expressed genes) in individual PNECs (n=176). Histogram shows number of PNECs observed with the pattern of sensory gene expression below it. Values at right are percent of PNECs (NE) and other (non-NE) profiled cells that express the gene and the mean expression level for expressing PNECs. Sensory genes are grouped by modality: mechanosensing (Mech); thermosensing (Δ); oxygen sensing (O2); acid-sensing (Acid); CO2-sensing, carbonic anhydrases (CO2), chemosensing (Chemo). Note the 56 different combinations of expressed sensory genes, with most PNECs predicted to be multimodal because they express more than one class of sensor. (B) Schematics of sensor and signal genes expressed by three individual PNECs. Number in center indicates sensory gene combination in panel A. Genes above number are expressed sensory genes, and genes below number are expressed signal genes with arrows indicating lung targets (cells that express receptor) or signals without identified lung targets that may enter circulation (circ) to target other organs.?, signals without known receptors. Imm, multiple immune populations; PSN, pulmonary sensory neurons.

Figure 5.

Figure 5—figure supplement 1. Mouse lung cell expression of sensory genes.

Figure 5—figure supplement 1.

(A) Heatmaps showing expression levels (ln (CPM + 1)) in individual PNECs (Neuroendocrine, n=176) and other lung cell types as indicated (see Figure 1—figure supplement 1). Sensory genes are grouped by sensory modality; only olfactory receptor genes (Olfr) expressed in PNECs are shown in heatmap. Genes of the NADPH oxidase complex previously proposed to participate in PNEC hypoxic response: Cybb/p91phos, Cyba/p22phox, Ncf2/p67phox, Rac2/Rho GTPase. Mcoln3, a TRP family channel, is also expressed in auditory hair cell stereocilia, but role in mechanosensation not established. (B) Heatmaps as above showing expression of voltage and ligand-gated potassium and calcium channels. K2P, potassium 2-pore channel; Kv, voltage-gated potassium channel; CNG-gated, cyclic nucleotide-gated channel; Ca2-act, calcium-activated channel. Note the many PNEC-specific ion channel genes identified including Kcnc3, Kcnk16, Kcnc1, Kcnc2, Kcnb1, Kcnv1, Kcnf1, Kcnq5, Kcnh2, Kcnh6, and Kcnh7. (C) Heatmap as above showing expression of opsin genes. MC, multiciliated cell; AT2, alveolar epithelial type 2cell; AT1, alveolar epithelial type 1cell; Stromal 1 and Stromal 2, stromal cell populations. Endo, endothelial cells; K2P, potassium 2-pore channels; Kv, voltage-gated potassium channels, CNG-gated, cyclic nucleotide-gated channels; Ca2+ act, calcium-activated channels.
Figure 5—figure supplement 2. Mouse lung cell expression of TNF family ligand and receptor genes.

Figure 5—figure supplement 2.

(A) scRNA-seq dot plots showing level of expression (dot intensity, ln (CPM + 1)) and percent of cells in population with detected expression (dot size) of TNF family receptor genes. Note PNEC (NE cell) expression of Tnfrsf12a (orange highlight) and Tnfrsf21 (blue). (B) scRNA-seq dot plots showing expression as above of TNF ligands. Note the expression of cognate ligands for the TNF receptors expressed in PNECs, Tnfsf12 (orange, ligand of Tnfrsf12a) and App (blue, ligand of Tnfrsf21). Cell types: NE, neuroendocrine (PNECs); AT1, alveolar epithelial cell, type 1; AT2, alveolar epithelial cell, type 2; Sm.M, smooth muscle; MyoF, myofibroblast; AdvF, adventitial fibroblast; AlvF, alveolar fibroblast; Peri, pericyte; Meso, mesothelial; Chondro, chondrocyte; Cap-a, capillary aerocyte; Cap, general capillary (Cap-g); Lym, lymphatic cell; B ZBTB32, B cells (ZBTB32+); Reg T, T cells (regulatory); T LY6G5B, T cells (LY6G5B+); NK, natural killer; T Alox5+, T cells (Alox5+); Neut, neutrophil; Baso, basophil; AlvMP, alveolar macrophage; IntMP, interstitial macrophage; pDC, plasmacytoid dendritic; mDC1, myeloid dendritic, type 1; mDC2, myeloid dendritic, type 2; CCR7+ DC, dendritic cell (Ccr7+); Mono(Class), monocyte (classical); Mono(NC), monocyte (non-classical); Mono(Int), monocyte (intermediate).