A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates
Peng He, Kyungtae Lim, Dawei Sun, Jan Patrick Pett, Quitz Jeng, Krzysztof Polanski, Ziqi Dong, Liam Bolt, Laura Richardson, Lira Mamanova, Monika Dabrowska, Anna Wilbrey-Clark, Elo Madissoon, Zewen Kelvin Tuong, Emma Dann, Chenqu Suo, Isaac Goh, Masahiro Yoshida, Marko Z. Nikolić, Sam M. Janes, Xiaoling He, Roger A. Barker, Sarah A. Teichmann, John C. Marioni, Kerstin B. Meyer, Emma L. Rawlins
Abstract
We present a multiomic cell atlas of human lung development that combines single-cell RNA and ATAC sequencing, high-throughput spatial transcriptomics, and single-cell imaging. Coupling single-cell methods with spatial analysis has allowed a comprehensive cellular survey of the epithelial, mesenchymal, endothelial, and erythrocyte/leukocyte compartments from 5–22 post-conception weeks. We identify previously uncharacterized cell states in all compartments. These include developmental-specific secretory progenitors and a subtype of neuroendocrine cell related to human small cell lung cancer. Our datasets are available through our web interface (https://lungcellatlas.org). To illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signaling and transcription factor hierarchies which we rigorously test using organoid models.
Datasets
1. All cells
Metadata
batch
dissection
chemistry
leiden
phase
big_cluster
broad_celltype
assay_ontology_term_id
cell_type_ontology_term_id
development_stage_ontology_term_id
disease_ontology_term_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sex_ontology_term_id
tissue_ontology_term_id
donor_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
5891STDY90308106141 cells WSSS_F_LNG87131874312 cells WSSS_F_LNG87131863794 cells 5891STDY90308093089 cells 5891STDY90308073045 cells WSSS_F_LNG87131793042 cells 5891STDY90308083015 cells 5891STDY80623542982 cells WSSS_F_LNG87131802919 cells 5891STDY90308062521 cells WSSS_F_LNG87131842509 cells WSSS_F_LNG87131772415 cells WSSS_F_LNG87131762403 cells WSSS_F_LNG87131852400 cells WSSS_F_LNG87131782212 cells WSSS_F_LNG87131881769 cells WSSS_F_LNG87131811768 cells WSSS_F_LNG87131911737 cells 5891STDY80623551673 cells 5891STDY80623531594 cells 5891STDY80623511422 cells 5891STDY80623491421 cells WSSS_F_LNG87131901185 cells WSSS_F_LNG8713189817 cells Distal epithelial6582 cells Proximal epithelial4155 cells Vas endothelial2793 cells Lymph endothelial1039 cells HsapDv:000005513170 cells HsapDv:000005912217 cells HsapDv:000005212071 cells NCBITaxon:960671752 cells UBERON:000204871752 cells fibroblast of lung22491 cells pulmonary interstitial fibroblast8289 cells epithelial cell of lung5943 cells tracheobronchial smooth muscle cell2903 cells capillary endothelial cell2259 cells lung ciliated cell1641 cells respiratory epithelial cell1423 cells classical monocyte1258 cells natural killer cell1184 cells endothelial cell of lymphatic vessel1039 cells myofibroblast cell848 cells CD16-negative, CD56-bright natural killer cell, human752 cells CD16-positive, CD56-dim natural killer cell, human687 cells precursor B cell650 cells vascular associated smooth muscle cell647 cells CD4-positive, alpha-beta T cell638 cells smooth muscle cell549 cells large pre-B-II cell546 cells small pre-B-II cell453 cells lung neuroendocrine cell440 cells CD8-positive, alpha-beta T cell405 cells mesothelial cell404 cells non-classical monocyte403 cells type II pneumocyte382 cells vein endothelial cell337 cells mesenchymal cell324 cells bronchus fibroblast of lung309 cells primitive red blood cell305 cells type I pneumocyte283 cells mature NK T cell270 cells regulatory T cell253 cells dendritic cell, human198 cells Schwann cell precursor192 cells endothelial cell of artery170 cells T-helper 17 cell167 cells group 2 innate lymphoid cell149 cells group 3 innate lymphoid cell135 cells lung secretory cell128 cells plasmacytoid dendritic cell125 cells CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human80 cells immature Schwann cell33 cells granulocyte monocyte progenitor cell29 cells hematopoietic stem cell29 cells megakaryocyte-erythroid progenitor cell28 cells early lymphoid progenitor21 cells neural progenitor cell15 cells squamous epithelial cell11 cells common myeloid progenitor7 cells 18th week post-fertilization human stage13170 cells 22nd week post-fertilization human stage12217 cells 15th week post-fertilization human stage12071 cells 11th week post-fertilization human stage9531 cells 9th week post-fertilization human stage8280 cells 20th week post-fertilization human stage7490 cells Carnegie stage 194790 cells Carnegie stage 164203 cells 2. Organoid
Metadata
batch
transgene
phase
leiden
predicted_hi
new_celltype
phenotype
Souporcell3_status
Souporcell3_assignment
dissection
chemistry
old_celltype
project
assay_ontology_term_id
cell_type_ontology_term_id
development_stage_ontology_term_id
disease_ontology_term_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sex_ontology_term_id
tissue_ontology_term_id
donor_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
WSSS_F_LNG1028202110073 cells WSSS_F_LNG102820259366 cells WSSS_F_LNG102820279126 cells WSSS_F_LNG102820268805 cells WSSS_F_LNG102820248538 cells WSSS_F_LNG102820205951 cells WSSS_F_LNG102820235529 cells WSSS_F_LNG102820224011 cells 5891STDY90308092049 cells 5891STDY90308081990 cells WSSS_F_LNG87131881013 cells WSSS_F_LNG8713191832 cells WSSS_F_LNG8713190582 cells WSSS_F_LNG8713189569 cells WSSS_F_LNG8713180199 cells WSSS_F_LNG8713178149 cells WSSS_F_LNG8713181143 cells WSSS_F_LNG8713179133 cells WSSS_F_LNG871318789 cells WSSS_F_LNG871317762 cells WSSS_F_LNG871317657 cells WSSS_F_LNG871318653 cells WSSS_F_LNG871318453 cells WSSS_F_LNG871318539 cells GRHL+ neuroendocrine C113181 cells Esophagus TRH+ epithelial C19906 cells Pulmonary neuroendocrine C13744 cells Proximal basal C1748 cells Promonocyte-like C2653 cells Ciliated-club doub C1516 cells Goblet-ciliated C6271 cells Basal-goblet-ciliated doub C6234 cells Early airway progenitor C1195 cells FBLN2- venous endo C3145 cells S100A12-hi cla. mono. C262 cells Adventitial fibro-epithelial doub C117 cells Promyelocyte-like C27 cells Secretory progenitors C17 cells HMOX1+ primitive erythroblast C33 cells LowQ embryonic cap-g C32 cells Airway SMC-epithelial doub C12 cells Fibro-endo doub C01 cells Schwann precursor C71 cells SCG3+ lymphatic endothelial C31 cells Definitive reticulocyte C31 cells HighM fetal fibro C01 cells HighM lymphatic endo C31 cells GHRL+ NE precursor11341 cells Pulmonary NE precursor2098 cells Mid airway progenitor838 cells Early airway progenitor436 cells Pulmonary neuroendocrine226 cells Late airway progenitor195 cells GHRL+ neuroendocrine77 cells NEUROD1+ pulmonary neuroendocrine50 cells Secretory progenitors39 cells MUC5AC+ ASCL1+ progenitor37 cells Default NEUROG38097 cells APOBEC3G+ETV7+ ΔNp63α4623 cells TCEA3+CRABP1+ PAX93354 cells SCGB1C1+ NEUROD13328 cells EGLN3+CA9+ Ctrl3185 cells SPARC+TNNT2+NOTCH1+ NEUROD11564 cells TCF7L1+NOTCH1+ ASCL11535 cells FAM3D+CCDC78+ RFX61523 cells ENO2+SERPINE1+ ΔNp63α1480 cells ΔNp63α-like TFAP2A1280 cells NGFR+CDH24+ RFX6284 cells AZGP1+POU2F3+ TFAP2A222 cells IGFBP5+FBLN1+ NEUROD/G134 cells MTTP+ early secretory cell C2383 cells Early tip cell C2366 cells low-quality ATs C2190 cells Neuroendocrine cell C274 cells KRT13+ suprabasal cell C256 cells Unknown GHRL+ cell C241 cells Unknown B-like epithelial cell C216 cells Unknown SFRP2+ cell epithelial cell C22 cells Unknown epithelial-like cell C01 cells Unknown AT-like cell C11 cells Unknown SMC-like epithelial cell 2 C21 cells Unknown low-quality fibroblast cell C01 cells NCBITaxon:960670495 cells UBERON:000204870495 cells epithelial cell of lung53439 cells neuroendocrine cell13742 cells respiratory epithelial cell1469 cells type II pneumocyte521 cells type I pneumocyte283 cells lung secretory cell128 cells lung neuroendocrine cell50 cells 11th week post-fertilization human stage2110 cells 9th week post-fertilization human stage2045 cells 15th week post-fertilization human stage1729 cells 18th week post-fertilization human stage1570 cells 22nd week post-fertilization human stage656 cells Carnegie stage 16412 cells Carnegie stage 19399 cells 20th week post-fertilization human stage175 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/2d2e2acd-dade-489f-a2da-6c11aa654028
Alias names
E-MTAB-11278, PMID36493756
Cite this study
He, P., Lim, K., Sun, D., Pett, J.P., Jeng, Q., Polanski, K., Dong, Z., Bolt, L., Richardson, L., Mamanova, L. and Dabrowska, M., 2022. A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates. Cell, 185(25), pp.4841-4860. https://doi.org/10.1016/j.cell.2022.11.005
