摘 要
肺癌是第二常见的癌症,也是全球癌症相关死亡率的主要原因。肿瘤生态系统具有多种免疫细胞类型。特别是髓样细胞很普遍,在促进疾病方面发挥着公认的作用。在我们的研究中,我们通过单细胞和空间转录组学分析了25名腺癌和鳞状细胞癌初治患者的约90万个细胞。我们注意到抗炎巨噬细胞和NK细胞/T细胞之间存在负相关关系,并且肿瘤内NK细胞的细胞毒性降低。虽然我们在腺癌和鳞状细胞癌中观察到相似的细胞类型组成,但我们检测到各种免疫检查点抑制剂的共表达存在显著差异。此外,我们揭示了肿瘤中巨噬细胞转录“重编程”的证据,将其转移到胆固醇输出,并采用促进铁外流的胎儿样转录特征。我们的多组学资源提供了肿瘤相关巨噬细胞的高分辨率分子图谱,加深了我们对它们在肿瘤微环境中作用的理解。
数据收集
scRNA-seq (N=24 patients)
Visium (N=8 patients)
软件使用
单细胞分析软件包列表
软件包名称 |
主要应用领域 |
官方链接 |
---|---|---|
CellRanger | 单细胞RNA测序原始数据处理 |
10x Genomics |
Harmony | 多数据集批次校正与整合 |
GitHub |
DropletUtils | 液滴数据质控与空滴检测 |
Bioconductor |
Scanpy | Python单细胞分析全流程 |
官方网站 |
Seurat | R语言单细胞分析标准工具包 |
官方网站 |
Scrublet | 双细胞检测与过滤 |
GitHub |
harmonypy | Python版Harmony批次校正 |
GitHub |
harmonyR | R语言版Harmony批次校正 |
GitHub |
scArches | 单细胞参考图谱映射与迁移学习 |
GitHub |
CellPhoneDB | 细胞间通讯网络分析 |
GitHub |
DESeq2 | 差异基因表达分析(伪bulk模式) |
Bioconductor |
Pegasus | 大规模单细胞云端分析平台 |
官方网站 |
PAGA | 细胞轨迹与分化路径推断 |
GitHub |
CopyKAT | 肿瘤细胞拷贝数变异检测 |
GitHub |
cell2location | 空间转录组细胞类型定位 |
GitHub |
关键应用场景
数据预处理
CellRanger
: 原始测序数据处理DropletUtils
: 液滴数据质控Scrublet
: 双细胞过滤
数据整合
-
Harmony
/harmonypy
/harmonyR
: 批次校正scArches
: 参考图谱整合
核心分析
-
Scanpy
/Pegasus
: 标准化分析流程Seurat
: 双细胞过滤DESeq2
: 差异表达分析PAGA
: 发育轨迹重构CopyKAT
: 肿瘤异质性分析
高级应用
-
CellPhoneDB
: 细胞互作网络cell2location
: 空间位置解析
统计方法
Wilcoxon rank-sum test
Wilcoxon signed-rank test
a two-sided Bonferroni correction
实验方法
Immunohistochemistry (IHC) and neutral lipid staining
Multiplexed Immunofluorescence
Image analysis
研究成果
1.单细胞转录组学揭示非小细胞肺癌的异质性
A 研究概述。
B 队列概述。
C UMAP投影和组合背景+健康数据集。
D 用于肿瘤样本中广泛细胞类型注释的代表性基因的点图。
E 等值线图显示了AT2细胞、CAML和AIMɸ中髓系和上皮基因的共表达。
F 盒图显示AT2细胞、CAML和AIM中髓系和上皮基因的正常化、标度化和对数转化的基因表达。
G 在CD235富集范围内计算的肿瘤和背景中非免疫细胞亚群的相对比例。
2.整合的单细胞和空间转录组学揭示了LUAD和LUSC中不同的相互作用网络
A 整合的单细胞和空间转录组学揭示了LUAD和LUSC中不同的相互作用网络。
B 热图显示了LUAD和LUSC中广泛的细胞注释总结的所有细胞类型之间的LR相互作用数量。
C ICI在LUAD和LUSC中的肿瘤特异性相互作用。
D 突出显示的ICI基因和细胞类型的点图。
E VEGFA/B相互作用物在LUAD和LUSC中的肿瘤特异性相互作用。
F EGFR相互作用物在LUAD和LUSC中的肿瘤特异性相互作用。
3.10x Visium证实了关键配体-受体对的空间共定位
A 一张空间图像描绘了代表性肿瘤切片上AT2细胞、AIM和Tregs的细胞丰度。
B 根据肿瘤和背景切片中细胞2位置的细胞丰度估计计算的免疫和非免疫细胞类型的相对比例。
C 空间LR共定位热图。
D 方框图显示了在所分析的每个切片中,肿瘤与背景中结肠定位LR对的频率存在显著差异。
E 空间图像描绘了NRP1-VEGFA、NECTIN2-TIGIT、PD1-PDL1、CD96-NECTIN1和HAVCR2-LGALS9在肿瘤和背景中发现LR对共表达的斑点位置。
4.CAML与肿瘤细胞共享肿瘤CNA和结肠
A CNA分析(cancer-associated macrophage-like cells,CAML)。
B PAGA图叠加在为肿瘤中的非免疫细胞类型计算的扩散图上。
C 前三个面板指示肿瘤浸润区域、Visium斑点上肿瘤区域的分箱和通过QC的斑点。
D 使用clusterProfiler R软件包对GO和REACTOME数据库进行过表示分析。
E 患者的AT2和CAML中CNA的详细概述。
F 肿瘤数据集中每种细胞类型之间损失和增益的KL散度散点图,使用其增益和损失分布计算。
G 空间图像描绘了三个代表性肿瘤切片上AT2细胞和CAML的细胞丰度。
H 在所有肿瘤切片中通过QC的斑点上,根据细胞类型组成计算的相关距离的分层聚类。
I 非负矩阵因子化建立在q05对所有肿瘤切片中通过QC的点的细胞类型丰度的估计之上。
5.肿瘤巨噬细胞经历癌胚重编程
A 使用py_DESeq2包提取的肿瘤中AIMɸ的DEGs与背景的火山图。
B GO注释M和AIM上调的DEGs。
C 肿瘤和背景组织切片上CD68和中性脂质的IHC。
D 肿瘤和背景切片中BODIPY信号覆盖的区域。
E 肿瘤(左)和背景(右)组织切片上CD68和STAB1的IHC。
F CD68+巨噬细胞群中STAB1+细胞的定量。
G 肿瘤组织切片上CD68、STAB1和PanCK的染色。
H NSCLC中CD68+巨噬细胞群内STAB1+CD68+细胞的定量。
I 点图显示了肿瘤中所有巨噬细胞亚群和CAML中STAB1特征基因”的表达。
J 肿瘤中肺泡Mφ与STAB1 Mφ的DEGs火山图。
K GO富集分析。
6.STAB1+Mɸ进行癌胚重编程
A 对协调(肿瘤髓系+背景髓系+胎儿肺髓系)PC空间中每个细胞计算的相关距离进行分层聚类。
B Violin图显示了在公开的人类胎儿肺图谱中鉴定的髓系细胞和祖细胞群体中STAB1基因特征的表达水平。
C 选定胎儿肺巨噬细胞群中STAB1基因特征中每个基因表达的点图。
D Violin图显示了在公开可用的MoMac VERSE数据集中鉴定的簇中STAB1基因特征的表达水平。
E 来自MoMacVERSE的选定巨噬细胞群中STAB1基因特征”中每个基因表达的点图。
F Violin图显示了在公开的“MoMac VERSE”数据集中鉴定的髓系细胞和祖细胞群体中AMɸ基因特征的表达水平。
G Violin图显示了在公开的人类胎儿肺图谱中鉴定的髓系细胞和祖细胞群体中AMɸ基因特征的表达水平。
H “MoMac VERSE”数据集中确定的选定巨噬细胞群体中AM基因特征中每个基因表达的点图
I 选定胎儿肺巨噬细胞群中AMɸ基因特征中每个基因表达的点图。
Reference
Cui, X., Liu, S., Song, H. et al. Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer. Mol Cancer 24, 111 (2025).
肺组织相关细胞和markers
Lung<-read.table("../Human_Lung.txt",sep="\t",header = T) knitr::kable(Lung[,3:4])
CellType
Marker
Activated CD4-positive, alpha-beta T cell
CTLA4, IL2RA
Adult endothelial progenitor cell
C7, CCL4, CCL5, CLU, CXCL2, FCN3, HPGD, NKG7, POSTN
Alpha-beta T cell
CD3E, CD40LG, IL7R
Alternatively activated macrophage
CCL18, IL10, ADORA3, C1QA, C1QB, CD163, CD209, CD68, IL4I1, IRF4, MARCO, MMP12, MRC1, SOCS3, STAT6, WNT5A
Alveolar capillary type 2 endothelial cell
HPGD
Alveolar macrophage
CD68, FABP4, FOLR3, MARCO, APOC1, C1QA, C1QB, CBX5, FBP1, FGFR2, GSN, LYZ, MME, MRC1, MSR1, NMB, NUBP2, PPARG
Alveolar monocyte
ALOX5AP, APOC1, APOE, GPNMB, INHBA
Anterior foregut endoderm cell
CPM
B cell
CD79A, CD19, MS4A1, CD79B, IGHM, CD24, IGKC, MZB1, IGHG1, IGLL5, JCHAIN, BANK1, BLK, IGHA1, IGHG3, PAX5, SDC1, CD68, CD74, CR2, DERL3, FAM30A, FCRL2, FCRL5, IGHG4, IGLC3, IGLV3-1, PNOC, PTPRC, SPIB, TCL1A, TNFRSF13C, TNFRSF17
Basal cell
KRT5, TP63, KRT14, KRT17, KRT13, NGFR, DAPL1, IL33, S100A2, ITGA6, KRT15, KRT8, LAMB3, APOC1, APOE, BCAM, BMP7, CD44, CTNNB1, DST, EMP3, G0S2, ITGB, ITGB4, KRT6A, LAMA3, LAMC2, LGALS1, MIR205HG, MKI67, NPPC, PDPN, SOX2, SYT8, TOB1, VIM
Basophil
CPA3, MS4A2, TPSAB1, CCR5, SMAD1
Brush cell
ASCL2, DCLK1, ALOX5AP, GNG13, IRAG2, POU2F3, RGS13, TRPM5
Cancer-associated fibroblast
COL1A1, COL1A2, FAP, THY1, COL6A1, COL6A2, COL6A3, DCN
Capillary endothelial cell
CA4, CD36, PRX, RGCC, SGK1, SPARC
CD14-low, CD16-positive monocyte
FCGR3A, MS4A7
CD14-positive monocyte
S100A8, CD14, CPVL, LYZ, S100A12, S100A9, VCAN
CD16-negative natural killer cell
CD160, GNLY, NKG7
CD16-positive natural killer cell
FCGR3A, GNLY, NKG7
CD4-intermediate, CD8-positive double-positive thymocyte
CCR9, SATB1, TOX2
CD4-positive, alpha-beta T cell
CD3E, CD8A, CD8B, COTL1, LDHB, CD4, CD3D
CD8-positive, alpha-beta cytotoxic T cell
CD3D, CD8A, GNLY, CD8B, GZMB, PRF1
CD8-positive, alpha-beta exhausted T cell
HAVCR2, CXCL13, ENTPD1, LAG3
CD8-positive, alpha-beta T cell
CD8A, CD3E, DUSP2, GZMK, CD8B, MKI67, CCL5, CCNA2, CD3D, GZMA, GZMB, ITGAE, NKG7, NUSAP1
Central memory CD4-positive, alpha-beta T cell
CCR7, CD4, SELL
Central memory CD8-positive, alpha-beta T cell
CCR7, CD8A, SELL
Central memory T cell
CCR7, IL7R, SELL
Cholangiocyte
EPCAM, KRT19, KRT7
Ciliated cell
FOXJ1, CAPS, CCDC78, TPPP3, TP73, TUBB1, C20orf85, CETN2, EPCAM, MUC5AC, PIFO, RFX2, TEKT1, TMEM190, TUBA1A
Ciliated epithelial cell
CAPS, CDHR3, CIBAR2, DNAH5, DNAI1, DNAI2, FOXJ1, HYDIN, RFX2, TPPP3, TUBA1A
Classical monocyte
CD14, S100A8, S100A12, S100A9
Club cell
SCGB1A1, SCGB3A2, SCGB3A1, CCKAR, MUC5B, BPIFB1, BPIFA1, CP, GABRP, PIGR, SLC23A2, SLPI, TMEM45A, TSPAN8
Dendritic cell
CD1C, CCL17, CD1A, CD207, CD83, CLEC9A, IL3RA, ITGAE, ITGAX, LILRA4, CCL22, CD209, CLEC4C, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, THBD, CCL13, CCR6, CCR7, CD1E, CD68, CLEC10A, CYP2S1, FCER1A, HLA-DPA1, HLA-DPB1, HLA-DRA, HLA-DRB1, HSD11B1, IRF7, ITGAM, JCHAIN, MHC Class II, NDRG2, PACSIN1, PCX3CR1, PFLT3, PKIB, PTPRC, SEC11C, TCF4
Dendritic cell, human
CD1C, CLEC10A, FCER1A
Deuterosomal cell
CDC20B, DEUP1, FOXJ1, FOXN4
Early alveolar monocyte
GPNMB, IL7R, INHBA
Effector CD8-positive, alpha-beta T cell
CCL5, GZMB
Effector memory CD4-positive, alpha-beta T cell
AQP3, ITGB1, KLRB1
Effector memory CD8-positive, alpha-beta T cell
GZMK, CCL5, CD8A, CXCR6, GZMA, ITGA1, ITGAE
Effector memory CD8-positive, alpha-beta T cell, terminally differentiated
CX3CR1, GNLY, GZMB
Effector memory T cell
DUSP4, GZMA, GZMK, IFNG, PDCD1
Effector T cell
CX3CR1, FCGR3A, FGFBP2
Endothelial cell
PECAM1, CLDN5, VWF, CDH5, CD34, FLT1, EMCN, ESAM, KDR, MCAM, PLVAP, RAMP2, ABI3BP, ACKR1, ANXA3, AQP1, CAV1, CDC25B, DONSON, EPAS1, ERG, ESM1, HMGA1, INMT, LYVE1, NAPSA, NDRG4, NPR3, PAPSS2, RNF144B, SDC4, SELE, SELP, SEMA3F, SFTPA1, SFTPA2, SFTPB, SFTPC, SLCO4A1, SLPI, TMEM100
Endothelial cell of artery
GJA5, BMX, FBLN5, EFNB2, GJA4, HEY1, LTBP4, SEMA3G, SOX17
Endothelial cell of lymphatic vessel
PROX1, CCL21, LYVE1, PDPN, FLT4, ACTA2, CNN1, MMRN1, RELN, RGS5, TAGLN, VWF
Endothelial cell of vascular tree
BACE2, CD300LG, CLDN5, EPHB4, LDB2, NOSTRIN, PECAM1, PTPRB, RAMP3, VWF
Endothelial cell-endothelial to mesenchymal transition
AQP1, CAV1, DCN, EPAS1, FN1, LUM, SPARC
Eosinophil
SIGLEC8, RNASE3
Epithelial cell
CDH1, EPCAM, KRT19, KRT18, KRT8, CAPS, CLDN4, KRT5, KRT7, MUC1, SFTPB, FOLR1, FXYD3, KRT14, KRT15, KRT17, KRT6A, KRT78, KRT80, SEC61G, SFTA2, SFTA3, SNTN, UPK3B, AGER, ANPEP, CAV1, CD1D, CD24, CLDN5, CLDN6, COL4A1, EMP2, FLT1, FOXJ1, IL6R, IL6ST, ITGAE, KRT1, KRT10, KRT12, KRT13, KRT16, KRT2, KRT20, KRT23, KRT24, KRT25, KRT26, KRT27, KRT28, KRT3, KRT31, KRT32, KRT33A, KRT33B, KRT34, KRT35, KRT36, KRT37, KRT38, KRT39, KRT4, KRT40, KRT6B, KRT6C, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77, KRT79, KRT81, KRT82, KRT83, KRT84, KRT85, KRT86, KRT9, MUC16, MUC5AC, NOS2, OSMR, PIFO, RAMP2, S100A2, SCGB1A1, SDC1, SFN, SFTPA1, SFTPC, SLPI, THBD, TMEM190, TP63, VCAM1
Epithelial fate stem cell
LGR6
Epithelial progenitor cell
CEACAM6
Erythrocyte
HBB, HBA1, HBA2, ALAS2, DNASE1L3, SLC25A37
Exhausted T cell
LAG3, CXCL13, HAVCR2, LAYN, PDCD1, PRDM1, TIGIT
Fat cell
ACSL1, ADIPOQ, EBF1, FOXO1, G0S2, GHR, LPIN1, PLIN1, PLIN2, PPARG
Fibroblast
COL1A1, DCN, PDGFRA, COL1A2, THY1, BGN, C1R, LUM, APOE, PLIN2, ACTA2, ACTG2, CFD, COL10A1, COL11A1, COL14A1, COL3A1, COL4A1, DPT, FABP5, FAP, FBLN1, ITGA8, PDGFRB, PTGDS, TCF21, VIM, A2M, ADGRE5, ANGPT1, APOD, ASPN, CCN2, CD36, COL18A1, COL5A1, COL5A2, COL6A1, COL6A2, COL6A3, COL6A6, COX4I2, CTSK, DDR2, DES, FABP4, FBN1, FLNB, FN1, GJA4, GSN, HGF, HIGD1B, HTRA3, IGFBP3, IGFBP5, IL33, IL6, LIPA, LPL, MCAM, MFAP5, MGP, MMP11, MMP2, MT2A, MYL9, MYLK, NDUFA4L2, NEGR1, NOTCH3, NXF1, OSMR, PDGFRL, PDPN, PI16, PPP1R14A, PTN, PTP4A3, PTPN13, RGS5, SEC14L2, SFRP4, SLIT2, SULF1, USO1, VCAN, VEGFD
Follicular B cell
CD40, CD69, MS4A1
Glial cell
GFRA3
Goblet cell
MUC5AC, MUC5B, SPDEF, GABRP, LIPF, SCGB1A1, TFF1, TFF2
Granulocyte
CEACAM8, S100A12
Group 3 innate lymphoid cell, human
IL4I1, KIT, RORC
Helper T cell
CD4, CXCL13, GP1BA
Hepatocyte
ALB, HPR, MASP2
Hillock cell
KRT13, KRT4
Inflammatory macrophage
CXCL10, CALHM6, CD68, CXCL11, CXCL12, CXCL9, HLA-DR family, STAT1
Intermediate monocyte
CD14, FCGR3A, FCGR3B, S100A8
Kupffer cell
LYZ, MARCO, S100A8, S100A9
Langerhans cell
CD1A, CD1C, CD1E, FCER1A
Late alveolar monocyte
APOC1, APOE, INHBA
Lung ciliated cell
FOXJ1, CAPS, C20orf85, CDHR3, PIFO, TMEM190, ALDH3B1, ATP5IF1, CCDC78, CFAP126, DNAAF3, DNAH11, DNAH12, DNAH5, DNMBP, EPCAM, FAM183A, FOXK1, HOATZ, LRRIQ1, SNTN, TPPP3, TSPAN1, TUBB4B
Lung microvascular endothelial cell
CCL21, CDH5, PECAM1, VWF
Lung neuroendocrine cell
ASCL1, CHGA, CALCA, S100A12, HOXB5, INSM1, KRT8, SYP, UCHL1
Lymphatic endothelial progenitor cell
CCL21, FABP4, TFF3
Macrophage
CD68, CD14, MARCO, CD163, MSR1, CSF1R, MRC1, APOE, C1QA, FABP4, ITGAM, ITGAX, SPP1, C1QB, FCGR1A, FCGR3A, FCN1, FOLR2, CCL18, CCL2, CCR2, CD74, CD80, CD86, CX3CR1, LYZ, MCEMP1, MS4A4A, PCLAF, PTPRC, RNASE1, TREM2, CBX7, CCL13, CCL3L1, CD36, CD5L, CD69, CD83, CD84, CEBPB, CHI3L1, CPM, CRIP1, F13A1, FCER1G, FCGR3B, GLDN, HAMP, HLA class II, ICAM1, IL1RN, ITGAL, LGMN, LYVE1, MERTK, MMP9, MR1, MS4A6A, NUPR1, OSM, PLA2G7, RBPJ, RETNLB, RPS23, RPS24, RPS27, SELENOP, SLC11A1, SLC40A1, TFRC, UBB
Marginal zone B cell of lymph node
IGLL5
Mast cell
TPSAB1, CPA3, TPSB2, MS4A2, KIT, HDC, GATA2, HPGDS, CLU, PTGS1, RGS13, CD68, CD69, CMA1, CSF3R, CXCL8, CXCR2, ENPP3, FCER1A, FCGR3B, FFAR2, G0S2, PTPRC, S100A8
Mature NK T cell
CD3E, CD8A, FCER1G, TYROBP, CD3D, NCR3
Megakaryocyte
PF4, PPBP, NRGN, OST4, MDK, MVK
Melanocyte
MLANA, PMEL
Memory B cell
CD27, CR2, MS4A1, CD1C, CD24, CXCR3, FAS, IRF8
Memory T cell
CD69, CXCR6, IL7R, ITGAE, LTB, MYADM, PTPRC
Mesenchymal cell
PDGFRA, PDGFRB, VIM, COL1A2, COL3A1, DCN, POSTN, S100A4, SNAI1, SNAI2, TCF21, ZEB1, ZEB2
Mesothelial cell
MSLN, UPK3B, WT1, CDH2, KRT19
Migratory DC
CCL22, CCR7, FSCN1, LAMP3
Migratory dendritic cell
CCL17, CCL19, CCR7, BIRC2, BIRC3, CCL22, CD200, CD274, CD80, ENO3, FAS, FSCN1, IDO1, IL12B, IL4I1, LAMP3, MARCKS, PDCD1LG2, RELB, SOCS2, TRAF1
Monocyte
CD14, FCN1, CD68, FCGR3A, APOE, CCR2, CD163, CSF1R, CX3CR1, FCGR1A, ITGAM, ITGAX, MARCO, MCEMP1, MRC1, MSR1, S100A8, S100A9, LYZ, VCAN, CAMP, CCL2, CD24, CD300E, CD36, CD74, EREG, FN1, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, JARID2, LDHB, LGALS2, S100A12, STMN1
MregDC
CCL17, CCL22, CCR7, LAMP3
Myelocyte
CSTA, FTL, S100A8
Myeloid dendritic cell
CD1C, CD74, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DQB3, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, CLEC9A, LAMP3, PLD4, ADGRE1, CCR7, CD1A, CD1B, CD207, CD209, CD4, CD40, CD80, CD83, CD86, FCER1A, HLA-DR family, ITGA4, ITGAM, ITGAX, LY75, MHC Class II, NRP1, PDCD1LG2
Myofibroblast cell
ACTA2, COL1A1, PDGFRA, ELN, MYH11, PDGFRB, TAGLN, ACTG2, Calponin family, DES, FN1, LUM, MYL9, MYLK, PLN, RGS5, SPINT2
Naive B cell
CD69, CD80, CD86, FCER2
Naive T cell
PTPRC
Naive thymus-derived CD4-positive, alpha-beta T cell
CCR7, CD4, CD3E, LEF1, C1orf162, SELL, GPR183
Naive thymus-derived CD8-positive, alpha-beta T cell
CD8A, CD3E, CD8B, GZMB, GZMH, CCR7
Natural killer cell
NKG7, KLRD1, GNLY, KLRB1, KLRC1, NCR1, NCAM1, TYROBP, XCL2, CD3D, FGFBP2, KIR2DL3, SEC11C, XCL1, ASCL1, CALCA, CD160, CD8A, CX3CR1, FCGR3A, GZMA, GZMB, GZMH, IFNG, IL32, KLRA1P, KLRF1, NCR3, PRF1, UCHL1
Neuroendocrine cell
ASCL1, CALCA, CHGA
Neuron
ASCL1, CADM1, ELAVL4, GRP, MPZ, NNAT, S100B, STMN2, SYNGR1, TUBB2B
Neutrophil
FCGR3B, S100A8, S100A9, CSF3R, CXCR2, IFITM2, ADGRG3, ALPL, CEACAM3, CEACAM8, CMTM2, CXCL8, CXCR1, FCAR, FFAR2, FPR1, G0S2, ITGAM, MME, MMP25, PROK2, S100A12, SIGLEC5, TNFRSF10C
Non-classical monocyte
FCGR3A, FCGR3B, C1QA, CX3CR1
Parasympathetic neuron
SNAP25
Pericyte
PDGFRB, CSPG4, TRPC6, RGS5, ACTA2, ANPEP, COX4I2, DES, GUCY1B1, HIGD1B, KCNK3, MCAM, MYO1B
Plasma cell
JCHAIN, CD79A, IGKC, CD27, IGHG4, SLAMF7, IGHA1, IGHG1, CD68, CD9, IGHA2, IGHG2, IGHG3, IGLC2, MZB1, PTPRC, SDC1, TNFRSF17, XBP1
Plasmablast
XBP1, IRF4, JCHAIN, MZB1, PRDM1
Plasmacytoid dendritic cell
LILRA4, CLEC4C, IRF8, LILRB4, IL3RA, IRF7, LRRC26, SCT, CXCR3, DNASE1L3, GZMB, IDO1, IRF4, JCHAIN, LAMP5, MZB1, NRP1, PACSIN1, SHD, SLC32A1, TCF4, TCL1A, THBD, TLR7
Plasmacytoid dendritic cell, human
IL3RA, LILRA4, PLD4
Pneumocyte
CLDN18, SFTPA1, SFTPA2, SFTPC, AGER, AQP4, NAPSA, ACTA2, CAV1, COL1A1, COL3A1, CPM, CXCL14, DCN, DES, EMP2, FOLR1, LAMP3, MMP7, MYL9, MYLK, NKX2-1, PDGFRA, PEBP4, PGC, SFRP4, SFTPB, SFTPD
Pre-alveolar type-1 transitional cell
CLDN4, KRT8, LGALS1, LGALS3, SFN
Progenitor cell
TM4SF1, AGER, ATXN1, CAV1, CD34, MUC5B, NKX2-1, RTKN2, SCGB3A2
Pulmonary ionocyte
ASCL3, CFTR, FOXI1, FXYD6, ID3, JADE1, RARRES2, TMEM160, TPM1
Regulatory T cell
FOXP3, IL2RA, CTLA4, TNFRSF18, TNFRSF4, CCR7, CCR8, CD27, CD3E, CD40LG, IKZF4, TNFRSF9
Smooth muscle cell
ACTA2, TAGLN, DES, MYH11, CNN1, LGR6, MYL9, ACTG2, ACTN1, COL1A1, COL3A1, GUCY1A1, GUCY1B1, MMP11, MYL6, MYLK, MYOCD, OSMR, PALLD, PDGFRB, SMTN, VCL
Stratified epithelial cell
KRT19, KRT7, PIGR, WFDC2
Stromal cell
ACTA2, DCN, LUM, MGP, PDGFRB, PECAM1, VWF
Suprabasal cell
KRT5, KRT19, NOTCH3, TP63
T cell
CD3D, CD3E, CD3G, CD8A, TRAC, CD2, TRBC1, NKG7, TRBC2, CD28, CD4, CD69, CD8B, CCL5, CD27, FOXP3, GZMA, GZMB, GZMK, IL7R, LTB, PTPRC, CD247, CD6, CD68, CD96, CTLA4, GNG4, GNLY, IL2RA, IL32, KLRD1, MKI67, NCAM1, PDCD1, SH2D1A, SKAP1, THEMIS, TOP2A, TRAT1, ZNF683
T follicular helper cell
CXCR5, ICOS, PDCD1
T-helper 1 cell
TBX21, CCL5, CXCR3, IFNG, TNF
T-helper 17 cell
CCR6, IL7R, ZBTB16
Tip cell
ESM1, NID2
Tissue-resident macrophage
CCL4, CXCL10, CXCL11, FABP4, ISG15, ISG20
Type 1 conventional dendritic cell
CLEC9A, XCR1, BATF3, BTLA, CADM1, CCL19, CCL22, CCR7, CD1C, EBI3, IDO1, LGALS2, NDRG2
Type 2 conventional dendritic cell
CD1C, CD1E, CLEC10A, FCER1A, CD1A, NLRP3, SIRPA
Type I pneumocyte
AGER, PDPN, CAV1, HOPX, AQP5, CLIC5, EMP2, CDH1, KRT19, SFTPC, ABCA3, AQP4, EPCAM, GPRC5A, KRT7, RTKN2, SFTPB, SLPI, TJP1
Type II pneumocyte
SFTPC, SFTPB, SFTPA1, SFTPD, SFTPA2, LAMP3, MUC1, PGC, SLC34A2, NAPSA, SFTPA3, ABCA3, ETV5, EPCAM, LPCAT1, MDK, NKX2-1, AGER, ALPG, CD44, HHIP, SLPI, WFDC2
Vascular associated smooth muscle cell
ACTA2, CNN1, RGS5, TAGLN, LGR5, NOTCH3, PDGFRB
Vein endothelial cell
ACKR1, SELP, COL15A1, NR2F2, VCAM1, VWA1