Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing

Allison M. Greaney; Taylor S. Adams; Micha Sam Brickman Raredon; Elise Gubbins; Jonas C. Schupp; Alexander J. Engler; Mahboobe Ghaedi; Yifan Yuan; Naftali Kaminski; Laura E. Niklason

doi:10.1016/j.celrep.2020.03.004

Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing

Cell Reports ◽

10.1016/j.celrep.2020.03.004 ◽

2020 ◽

Vol 30 (12) ◽

pp. 4250-4265.e6 ◽

Cited By ~ 3

Author(s):

Allison M. Greaney ◽

Taylor S. Adams ◽

Micha Sam Brickman Raredon ◽

Elise Gubbins ◽

Jonas C. Schupp ◽

...

Keyword(s):

Single Cell ◽

Rna Sequencing ◽

Basal Cells ◽

Single Cell Rna Sequencing

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Using single-cell RNA sequencing to unravel cell lineage relationships in the respiratory tract

Biochemical Society Transactions ◽

10.1042/bst20191010 ◽

2020 ◽

Vol 48 (1) ◽

pp. 327-336 ◽

Cited By ~ 8

Author(s):

L.E. Zaragosi ◽

M. Deprez ◽

P. Barbry

Keyword(s):

Respiratory Tract ◽

Single Cell ◽

Rna Sequencing ◽

Cell Lineage ◽

Neuroendocrine Cells ◽

Basal Cells ◽

Multiciliated Cells ◽

Single Cell Rna Sequencing ◽

Rare Cells ◽

Genetic Labeling

The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, ‘hybrid’ mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

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Integrated single-cell RNA sequencing analysis reveals distinct cellular and transcriptional modules associated with survival in lung cancer

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00824-9 ◽

2022 ◽

Vol 7 (1) ◽

Author(s):

Li Zhang ◽

Yiming Zhang ◽

Chengdi Wang ◽

Ying Yang ◽

Yinyun Ni ◽

...

Keyword(s):

Lung Cancer ◽

Single Cell ◽

Rna Sequencing ◽

Squamous Carcinoma ◽

Specific Gene ◽

Sequencing Analysis ◽

Basal Cells ◽

Functional Roles ◽

Pathologic Features ◽

Single Cell Rna Sequencing

AbstractLung adenocarcinoma (LUAD) and squamous carcinoma (LUSC) are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms. The heterogeneity can be attributed to genetic, transcriptional, and epigenetic parameters. Here, we established a multi-omics atlas, integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing. We investigated their differences in genetic amplification, cellular compositions, and expression modules. We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells, and had distinct cellular composition modules associated with poor survival of lung cancer. Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression. Moreover, we identified subclusters with proliferating and differentiating properties in AT2 and basal cells. Overexpression assays of ten genes, including sub-cluster markers AQP5 and KPNA2, further indicated their functional roles, providing potential targets for early diagnosis and treatment in lung cancer.

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