scholarly journals A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates

2022 ◽  
Author(s):  
Peng He ◽  
Kyungtae Lim ◽  
Dawei Sun ◽  
Jan Patrick Pett ◽  
Quitz Jeng ◽  
...  
Keyword(s):  
Single Cell ◽  
Lung Development ◽  
Cell Imaging ◽  
Human Lung ◽  
Cell Signalling ◽  
Fetal Lung ◽  
Web Interface ◽  
General Utility ◽  
Single Cell Imaging ◽  
Human Fetal Lung

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 new cell states in all compartments. These include developmental-specific secretory progenitors that resemble cells in adult fibrotic lungs and a new subtype of neuroendocrine cell related to human small cell lung cancer; observations which strengthen the connections between development and disease/regeneration. Our datasets are available for the community to download and interact with through our web interface (https://fetal-lung.cellgeni.sanger.ac.uk). Finally, to illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signalling and transcription factor hierarchies which we test using organoid models.

scholarly journals Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk

Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 536
Author(s):  
Sunita Sharma ◽  
Alvin T. Kho ◽  
Divya Chhabra ◽  
Kathleen Haley ◽  
Carrie Vyhlidal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Development ◽  
Human Lung ◽  
Expression Profiles ◽  
Fetal Lung ◽  
In Utero ◽  
Differentially Expressed ◽  
Mouse Lung ◽  
Asthma Susceptibility ◽  
Human Fetal Lung

Background: In utero smoke (IUS) exposure is associated with asthma susceptibility. Objective: We sought to test the hypothesis that changes in miRNA expression by IUS exposure during human lung development is associated with asthma susceptibility. Methods: Gene expression was profiled from 53 IUS unexposed and 51 IUS exposed human fetal lung tissues. We tested for the differential expression of miRNAs across post-conception age and by IUS using linear models with covariate adjustment. We tested the IUS-associated miRNAs for association with their gene expression targets using pair-wise inverse correlation. Using our mouse model, we investigated the persistence of the IUS-associated miRNA signature using RT-PCR from the lungs of mouse pups with and without IUS at postnatal day 14. MiRNAs were then tested for association with asthma and exacerbations using whole blood gene expression profiles from Asthma BRIDGE. Results: Five miRNAs were differentially expressed across post-conception age (adjusted p < 0.0002) including two that were differentially expressed by IUS exposure in human fetal lung (p < 0.05). MiR-15a was differentially expressed by post-conception age (p = 0.00002), IUS exposure in human fetal lung (p = 0.005), and in the post-natal mouse lung (p = 0.01). MiR-15a was also associated with the in utero expression of GSDMB (adjusted p = 0.0002), a known childhood asthma gene and with asthma exacerbations (p = 0.0009) in Asthma BRIDGE. Thus, miR-15a is expressed during human lung development, is impacted by IUS exposure, regulates the intrauterine expression of asthma genes, and is associated with asthma severity. Conclusions: These results provide evidence for the role of miR-15a in the fetal origin of asthma.

Single Cell Imaging of Human Cologenic Carcinoma Cells by 3-Tesla MRI

2004 ◽  
Vol 176 (03) ◽  
Author(s):  
UKM Teichgräber ◽  
JG Pinkernelle ◽  
F Neumann ◽  
T Benter ◽  
H Bruhn ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Imaging ◽  
Carcinoma Cells ◽  
3 Tesla ◽  
Single Cell Imaging ◽  
3 Tesla Mri

Enabling drug discovery and development through single-cell imaging

2018 ◽  
Vol 14 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Andrea K. Pomerantz ◽  
Farid Sari-Sarraf ◽  
Kerri J. Grove ◽  
Liliana Pedro ◽  
Patrick J. Rudewicz ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Single Cell ◽  
Cell Imaging ◽  
Drug Discovery And Development ◽  
Single Cell Imaging

High-content screening of drug-induced cardiotoxicity using quantitative single cell imaging cytometry on microfluidic device

Lab on a Chip ◽  
2011 ◽  
Vol 11 (1) ◽  
pp. 104-114 ◽  
Author(s):  
Min Jung Kim ◽  
Su Chul Lee ◽  
Sukdeb Pal ◽  
Eunyoung Han ◽  
Joon Myong Song
Keyword(s):  
Single Cell ◽  
Microfluidic Device ◽  
Cell Imaging ◽  
High Content Screening ◽  
Drug Induced ◽  
Single Cell Imaging ◽  
Imaging Cytometry

scholarly journals MORPHOGENETIC ASPECTS OF MULTILAYERING IN PETRI DISH CULTURES OF HUMAN FETAL LUNG FIBROBLASTS

1969 ◽  
Vol 41 (1) ◽  
pp. 298-311 ◽  
Author(s):  
Tom Elsdale ◽  
Robert Foley
Keyword(s):  
Extracellular Matrix ◽  
Human Lung ◽  
Petri Dish ◽  
Fetal Lung ◽  
Single Species ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Spontaneous Aggregation ◽  
Control Hypothesis ◽  
Human Fetal Lung

Randomly seeded Petri dish cultures of embryonic human lung fibroblasts generate, in the course of their growth, highly ordered cellular arrangements. Thick, bilaterally symmetrical ridges with an axial polarity and an orthogonal, multilayered internal organization are observed within stationary cultures. The generation of these structures has been investigated. Ridges result from the spontaneous aggregation of cells in postconfluent cultures brought about by directed cell movements. These movements are promoted by the localized production of extracellular matrix sheets containing collagen, which provide new substrates for cellular colonization. Cells that have colonized one matrix substrate may secrete another above themselves, which will in turn be colonized. By a continuation of this cycle, thick stacks consisting of alternate layers of cells and matrix are produced to yield the observed aggregations. The distribution and shape of ridges in a culture imply that matrix substrates are confined to specific locations. The suggested control hypothesis assumes that all the cells in fibroblast cultures are potential producers of a single species of matrix. The serviceability of this matrix as a substrate for cellular colonization, however, is destroyed if the producer cells are motile. Matrix substrates, therefore, are only made by nonmotile cells.

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