Human distal airways contain a multipotent secretory cell that can regenerate alveoli

Basil, Maria C.; Cardenas-Diaz, Fabian L.; Kathiriya, Jaymin J.; Morley, Michael; Carl, Justine; Brumwell, Alexis; Katzen, Jeremy; Slovik, Katherine J.; Babu, Apoorva; Zhou, Shanshan; Kremp, Madison M.; McCauley, Katherine B.; Li, Shanru; Planer, Joseph D.; Hussain, Shah S.; Liu, Xiaoming; Windmueller, Rebecca; Ying, Yun; Stewart, Kathleen M.; Oyster, Michelle; Christie, Jason D.; Diamond, Joshua M.; Engelhardt, John F.; Cantu, Edward; Rowe, Steven M.; Kotton, Darrell N.; Chapman, Harold A.; Morrisey, Edward E.

doi:10.1038/s41586-022-04552-0

Cited by 141 publications

(150 citation statements)

References 62 publications

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“…The "CellRef" identified cell types mapped to the cell type nomenclature in the LungMAP CellCards 10 . In addition, based on unbiased clustering analysis, we identified cell types that are not yet included in the CellCards but reported in recent scRNA-seq analyses, including deuterosomal cells 14 , suprabasal cells 14 , systemic venous endothelial cells 19 , mature dendritic cell subset 20 , SMG duct cells 22 , respiratory airway secretory cells (RAS, a recently identified multipotent secretory cell population in respiratory bronchioles) 4 , and megakaryocyte/platelets 15,21 . During the "CellRef" construction, we discovered cell clusters selectively expressing marker genes of those new cell types, and thus we have included those cell types into the "LungMAP Human Lung CellRef".…”

Section: Discussionmentioning

confidence: 99%

“…Cells with consistent cell type annotations were combined with the "seeds" to form the "LungMAP Human Lung CellRef" (347,970 cells) (Figure 2B, Supplementary Figures 1-2 [Treg] cells). In addition to the known lung cell types, we extended the dictionary to incorporate 7 cell types that are not yet in the CellCards but have marker genes reported in recent scRNA-seq studies and selectively expressed in our unbiasedly identified cell clusters, including deuterosomal cells 14 (DEUP1, FOXN4, CDC20B), suprabasal cells 14 (SERPINB4, KRT19, NOTCH3), systemic venous endothelial cells 19 (SVEC; marker genes: COL15A1, ABCB1, ACKR1), mature dendritic cell subset 20 (maDC; marker genes: CCR7, CCL19, LAD1), megakaryocyte/platelets 15,21 (ITGA2B, ITGB3), SMG duct cells 22 (MIA, ALDH1A3, RARRES1), and respiratory airway secretory cells 4 (RAS; marker genes: SCGB3A2, KLK11, SOX4). We combined SMG basal and SMG duct cells into one mixed type, "SMG Basal/Duct cell", since their marker genes were co-expressed in the same cell cluster in our data integration.…”

Section: The Lungmap Human Lung Cellrefmentioning

confidence: 99%

“…were performed as described in Basil et al, 2022 4 . Sequencing read alignment to the hg38 human genome and UMI matrix generation were performed for each sample using 10x Cell Ranger v3 software.…”

Section: Collection and Pre-processing Of Single Cell/single Nucleus ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Single cell RNA-seq (scRNA-seq) analysis is being widely applied to biomedical research, enabling the study of complex organs, such as the lung, at unprecedented scale and resolution, and transforming our understanding of organ development and disease 1-4 . Accurate cell type identification is a key and rate-limiting step in the single cell data analysis that usually requires time-consuming processes to optimize computational parameters followed by manual inspections that require domain expertise.…”

Section: Introductionmentioning

confidence: 99%

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Guided construction of single cell reference for human and mouse lung

Guo

Morley

et al. 2022

Preprint

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Accurate cell type identification is a key and rate-limiting step in single cell data analysis. Single cell references with comprehensive cell types, reproducible and functional validated cell identities, and common nomenclatures are much needed by the research community to optimize automated cell type annotation and facilitate data integration, sharing, and collaboration. In the present study, we developed a novel computational pipeline to utilize the LungMAP CellCards as a dictionary to consolidate single-cell transcriptomic datasets of 104 human lungs and 17 mouse lung samples and constructed "LungMAP CellRef" and "LungMAP CellRef Seed" for both normal human and mouse lungs. "CellRef Seed" has an equivalent prediction power and produces consistent cell annotation as does "CellRef" but improves computational efficiency and simplifies its utilization for fast automated cell type annotation and online visualization. This atlas set incorporates 48 human and 40 mouse well-defined lung cell types catalogued from diverse anatomic locations and developmental time points. Using independent datasets, we demonstrated the utility of our CellRefs for automated cell type annotation analysis of both normal and disease lungs. User-friendly web interfaces were developed to support easy access and maximal utilization of the LungMAP CellRefs. LungMAP CellRefs are freely available to the pulmonary research community through fast interactive web interfaces to facilitate hypothesis generation, research discovery, and identification of cell type alterations in disease conditions.

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Section: Discussionmentioning

confidence: 99%

Section: The Lungmap Human Lung Cellrefmentioning

confidence: 99%

Section: Collection and Pre-processing Of Single Cell/single Nucleus ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Guided construction of single cell reference for human and mouse lung

Guo

Morley

et al. 2022

Preprint

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Roles of telocytes dominated cell–cell communication in fibroproliferative acute respiratory distress syndrome

Zheng,

Cai,

Zhao

et al. 2024

Clinical and Translational Dis

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Telocytes (TCs) are a new type of interstitial cell identified in multiple tissues of mammals, including the human lung, and mediate homocellular or heterocellular cell‐cell communication. Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure and combined with direct and indirect lung injury, which is induced by pneumonia, sepsis, burns, etc. Pulmonary fibrosis is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium and gets more and more attention as a well‐recognized sequela of ARDS or mechanical ventilation. However, the existing intervention measures could not prevent the progression of pulmonary fibrosis. Although the protective effect of TCs in acute lung injury had been demonstrated in both cellular and animal models in previous studies by our or other researchers, the roles of TCs mediated cell‐cell communication in fibroproliferative ARDS is unclear. This review is aimed at integrating our understanding of TC‐mediated cell–cell communication in lung diseases with pulmonary fibrosis after ARDS.

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Lung regeneration: diverse cell types and the therapeutic potential

Chen,

Li,

et al. 2024

MedComm

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Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.

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Human distal airways contain a multipotent secretory cell that can regenerate alveoli

Cited by 141 publications

References 62 publications

Guided construction of single cell reference for human and mouse lung

Guided construction of single cell reference for human and mouse lung

Roles of telocytes dominated cell–cell communication in fibroproliferative acute respiratory distress syndrome

Lung regeneration: diverse cell types and the therapeutic potential

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