Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

2018 ◽  
Author(s):  
Rob Hynds
Keyword(s):  
Cell Differentiation ◽  
Single Cell ◽  
Rna Sequencing ◽  
Airway Epithelium ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Single Cell Rna Sequencing ◽  
Epithelium Regeneration

scholarly journals Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

2018 ◽  
Author(s):  
Sandra Ruiz Garcia ◽  
Marie Deprez ◽  
Kevin Lebrigand ◽  
Agnès Paquet ◽  
Amélie Cavard ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Airway Epithelium ◽  
Secretory Cells ◽  
Specific Cell ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Multiciliated Cells ◽  
Epithelium Regeneration ◽  
Cell Trajectories

AbstractBackgroundIt is usually considered that the upper airway epithelium is composed of multiciliated, goblet, secretory and basal cells, which collectively constitute an efficient first line of defense against inhalation of noxious substances. Upon injury, regeneration of this epithelium through proliferation and differentiation can restore a proper mucociliary function. However, in chronic airway diseases, the injured epithelium frequently displays defective repair leading to tissue remodeling, characterized by a loss of multiciliated cells and mucus hyper-secretion. Delineating drivers of differentiation dynamics and cell fate in the human airway epithelium is important to preserve homeostasis.ResultsWe have used single cell transcriptomics to characterize the sequence of cellular and molecular processes taking place during human airway epithelium regeneration. We have characterized airway subpopulations with high resolution and lineage inference algorithms have unraveled cell trajectories from basal to luminal cells, providing markers for specific cell populations, such as deuterosomal cells, i.e. precursors of multiciliated cells. We report that goblet cells, like secretory cells, can act as precursors of multiciliated cells. Our study provides a repertoire of molecules involved in key steps of the regeneration process, either keratins or components of the Notch, Wnt or BMP/TGFβ signaling pathways. Our findings were confirmed in independent experiments performed on fresh human and pig airway samples, and on mouse tracheal epithelial cells.ConclusionsOur single-cell RNA-seq study provides novel insights about airway epithelium differentiation dynamics, clarifies cell trajectories between secretory, goblet and multiciliated cells, identifies novel cell subpopulations, and maps the activation and repression of key signaling pathways.

Differentiated and functional human airway epithelium regeneration in tracheal xenografts

2000 ◽  
Vol 278 (1) ◽  
pp. L165-L176 ◽  
Author(s):  
F. Dupuit ◽  
D. Gaillard ◽  
J. Hinnrasky ◽  
E. Mongodin ◽  
S. de Bentzmann ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nude Mice ◽  
Airway Epithelium ◽  
Xenograft Model ◽  
Regeneration Process ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Human Nasal Epithelial Cells ◽  
Epithelium Regeneration ◽  
Well Differentiated

To investigate the regeneration process of a well-differentiated and functional human airway epithelium, we adapted an in vivo xenograft model in which adult human nasal epithelial cells adhere and progressively repopulate denuded rat tracheae grafted in nude mice. The proliferating activity, the degree of differentiation, and the barrier integrity of the repopulated epithelium were studied during the regeneration process at optical and ultrastructural levels with immunocytochemistry and a permeability tracer. Three days after implantation in nude mice, tracheal xenografts were partially repopulated with a flattened nonciliated and poorly differentiated leaky epithelium. By the end of the first week after the graft, cell proliferation produced on the entire surface of the rat trachea an epithelium that was stratified into multiple layers and tightly sealed. During successive weeks, cell proliferation dramatically decreased. Moreover, the epithelium became progressively columnar, secretory, ciliated, and transiently leaky. At 4–5 wk, a fully differentiated pseudostratified functional epithelial barrier impermeable to a low-molecular-weight tracer was reconstituted. The regeneration of a well-differentiated and functional human airway epithelium in rat tracheae grafted in nude mice includes several steps that mimic the regeneration dynamics of airway epithelium after injury.

scholarly journals VirtualCytometry: a webserver for evaluating immune cell differentiation using single-cell RNA sequencing data

2019 ◽  
Vol 36 (2) ◽  
pp. 546-551 ◽  
Author(s):  
Kyungsoo Kim ◽  
Sunmo Yang ◽  
Sang-Jun Ha ◽  
Insuk Lee
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cell Differentiation ◽  
T Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Immune Cell ◽  
Signaling Molecules ◽  
Single Cell Rna Sequencing ◽  
Functional States

Abstract Motivation The immune system has diverse types of cells that are differentiated or activated via various signaling pathways and transcriptional regulation upon challenging conditions. Immunophenotyping by flow and mass cytometry are the major approaches for identifying key signaling molecules and transcription factors directing the transition between the functional states of immune cells. However, few proteins can be evaluated by flow cytometry in a single experiment, preventing researchers from obtaining a comprehensive picture of the molecular programs involved in immune cell differentiation. Recent advances in single-cell RNA sequencing (scRNA-seq) have enabled unbiased genome-wide quantification of gene expression in individual cells on a large scale, providing a new and versatile analytical pipeline for studying immune cell differentiation. Results We present VirtualCytometry, a web-based computational pipeline for evaluating immune cell differentiation by exploiting cell-to-cell variation in gene expression with scRNA-seq data. Differentiating cells often show a continuous spectrum of cellular states rather than distinct populations. VirtualCytometry enables the identification of cellular subsets for different functional states of differentiation based on the expression of marker genes. Case studies have highlighted the usefulness of this subset analysis strategy for discovering signaling molecules and transcription factors for human T-cell exhaustion, a state of T-cell dysfunction, in tumor and mouse dendritic cells activated by pathogens. With more than 226 scRNA-seq datasets precompiled from public repositories covering diverse mouse and human immune cell types in normal and disease tissues, VirtualCytometry is a useful resource for the molecular dissection of immune cell differentiation. Availability and implementation www.grnpedia.org/cytometry

scholarly journals Revealing cellular and molecular transitions in neonatal germ cell differentiation using single cell RNA sequencing

Development ◽  
2019 ◽  
Vol 146 (6) ◽  
pp. dev174953 ◽  
Author(s):  
Jinyue Liao ◽  
Shuk Han Ng ◽  
Alfred Chun Luk ◽  
Hoi Ching Suen ◽  
Yan Qian ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Germ Cell Differentiation ◽  
Single Cell Rna Sequencing
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