Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung

ABSTRACT: Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13+ basal and Krt15+ club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung, Mesenchymal Cell

SUBMITTER: Claudia Scholl

LAB HEAD: Claudia Scholl

PROVIDER: PXD039508 | Pride | 2024-01-19

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	UP000000589_10090.fasta	Fasta
	checksum.txt	Txt
	qecf1-MH0245-1.raw	Raw
	qecf1-MH0245-2.raw	Raw
	qecf1-MH0245-3.raw	Raw

Items per page:

1 - 5 of 14

Similar Datasets

Single-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung

Project description:Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13+ basal and Krt15+ club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.

2024-01-16 | GSE223816 | GEO

Foxa2 programs Th2-cell mediated innate immunity in the developing lung.

Project description:Deletion of the gene encoding Foxa2, a winged helix transcription factor selectively expressed in respiratory epithelial cells, caused spontaneous pulmonary eosinophilic inflammation and goblet cell metaplasia. Loss of Foxa2 induced the recruitment and activation of myeloid dendritic cells (mDCs) and Th2 cells in the lung, and was associated with the increased production of T helper 2 (Th2) cytokines and chemokines. mRNA microarray analysis demonstrated that deletion of Foxa2 induced the expression of a number of mRNAs regulating pulmonary dendritic cell activation, Th2 mediated inflammation, and goblet cell differentiation. The spontaneous pulmonary inflammation and goblet cell metaplasia caused by loss of Foxa2 was inhibited by treatment of newborn Foxa2â??/â?? mice with monoclonal IL-4Ralpha antibody. Expression of Foxa2 in non-ciliated secretory cells (Clara cells) in vivo inhibited goblet cell differentiation induced by pulmonary allergen exposure. The respiratory epithelium plays a central role in the regulation of Th2-mediated inflammation and innate immunity in the developing lung in a process regulated by Foxa2. To investigate the role of Foxa2 and its downstream targets associated with the Th2 inflammation and goblet cell hyperplasia, RNAs were isolated from the lungs of Foxa2-/- and control littermates at PN15. Lung cRNA was hybridized to the murine genome MOE430 V2 chips.

2010-03-09 | E-GEOD-19204 | biostudies-arrayexpress

Wound epidermis-dependent transcriptional programs

Project description:The wound epidermis is required for limb regeneration. To elucidate the roles of the wound epidermis during early regeneration, we examined how the transcriptional programs of early dividing cells (enriched for blastemal progenitors) and non-dividing cells in regenerating stump tissues as well as epithelial cells change when we prevented wound epidermis formation.

2020-01-15 | GSE132317 | GEO

Single cell transcriptome analysis of adult murine lung airway epithelium after NAPH-induced injury

Project description:To comprehensively study how club cells response to airway epithelial injury, we performed single cell transcriptomic analysis of the normal and NAPH injured lung samples. Our analysis reveals that a previously undescribed pathway promoting mucous metaplasia that involves VEGFa and its receptor KDR. Our single cell RNA sequencing analysis revealed that VEGFR2 (also known as FLK1 or KDR) is expressed in club cell subpopulations. Loss of KDR, its ligand VEGFa, or downstream MEK/ERK causes excessive differentiation of club cells into mucous cells (mainly goblet cells) during development and regeneration following Naphthalene (NAPH) challenge.

2021-04-07 | GSE171571 | GEO

Spatial resolution of proteomic changes in lung tissue from a flexible AAV-DTR/DT mouse model of acute cell deletion mimicking epithelial lung injury

Project description:Lung epithelial injury leads to different pathologies, all associated with severe outcome and increased mortality. These pathologies are divided into chronic and acute diseases like idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) or the acute lung distress syndrome (ARDS). Hallmarks of both groups of lung diseases are a breakdown of the epithelial barrier and impairment of lung function. Repeated epithelial injury leads to chronic inflammation, fibroblast activation and ultimately to scarring and stiffening of the lung. The observed decline in lung function is the first symptom of IPF patients. As these changes are occurring slowly over time, patients only present to clinicians at a rather late stage. Therefore, disease driving mechanisms can only be estimated based on observed changes in biomarkers, the transcriptome or proteome. However, alterations in signalling pathways at a very early stage of disease development can only be investigated in vitro or in animal models. In this study a novel and flexible DTR/DT model of acute epithelial lung injury driven by AAV6.2 mediated human diphtheria toxin receptor (hDTR) expression was developed and characterized. The hDTR is sensitive for diphtheria toxin (DT), thereby inducing apoptosis by blocking protein synthesis. In contrast, a polymorphism of the murine DTR protects mice from DT mediated toxicity. The AAV6.2 variant transduces specifically into bronchial epithelial and alveolar epithelial type II cells leading to their depletion after DT administration. Using laser-capture microdissection different epithelial cell regions (bronchial epithelium and alveolar epithelium) were isolated from formalin-fixed and paraffin-embedded lung tissue of AAV-stuffer and AAV-hDTR mice, which were administered intratracheally with 100 ng DT for 24 h, and analyzed using mass spectrometry.

2022-06-30 | PXD025712 | Pride

An inflammatory memory of COVID-19 in airway basal stem cells impairs mucociliary differentiation (RNA-Seq)

Project description:Airway basal stem cells (BSCs) in chronic lung diseases accumulate memories to promote disease-specific pathogenesis. Whether acute lung infection also endows BSCs with an inflammatory memory to impair epithelial regeneration is unknown. Here, we derived multiple BSC lines from patients with and without COVID-19 (CoV19) using tracheal aspirate (TA) as a viable source of bronchial BSCs. While tested negative for SARS-CoV-2, BSC lines from CoV19 patients bore a proinflammatory gene signature, exhibited early cell cycle exist, and displayed goblet cell hypoplasia following differentiation in air-liquid interface (ALI). These phenotypes reproduced, at least partially, changes in BSCs in patients with CoV19 assessed by bioinformatic analysis of preexisting single cell transcriptomes of BSCs and by staining of lung sections for select markers. Such a memory in BSCs previously exposed to CoV19 was mediated by increases in chromosomal accessibility at key inflammatory gene loci associated with gene dysregulation and sustained STAT3 activation. Blockade of STAT3 hyperactivation in CoV19-exposed BSCs restored mucociliary differentiation in ALI. Taken together, BSCs acquire an epigenetic memory of CoV19 to impair epithelial regeneration. BSC derivation from TA provides a versatile approach to model airway epithelium in health and lung diseases.

2023-06-01 | GSE212411 | GEO

An inflammatory memory of COVID-19 in airway basal stem cells impairs mucociliary differentiation (ATAC-Seq)

2023-06-01 | GSE212410 | GEO

Transcription profiling ofmouse wild type and GATA6 null lung

Project description:Epithelial organs including the lung are known to possess regenerative abilities through activation of endogenous stem cell populations but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation in Gata6 null lung epithelium. This expansion of BASCs is the result of a dramatic increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the non-canonical Wnt receptor Fzd2 is down-regulated in Gata6 mutants and increased Fzd2 or decreased Î²-catenin expression rescues, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, we show that canonical Wnt signaling is activated in the niche containing BASCs and forced activation of Wnt signaling leads to a dramatic increase in BASC numbers. Moreover, Gata6 is required for proper lung epithelial regeneration and postnatal loss of Gata6 leads to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6 regulated Wnt signaling controls the balance between stem/progenitor expansion and epithelial differentiation required for both lung development and regeneration. Experiment Overall Design: 3 replicates of each condition-wild-type and GATA6 null tissue. 6 total samples.

2008-06-11 | E-GEOD-11165 | biostudies-arrayexpress

Effects of HSP90 inhibitors on airway goblet cell metaplasia

Project description:Goblet cell metaplasia and mucus hypersecretion are disabling hallmarks of chronic lung diseases for which no curative treatments are available. Therapies targeting specific upstream drivers of asthma have had variable results. We hypothesized that an a priori-knowledge independent approach would point to new therapies for airway goblet cell metaplasia. We analyzed the transcriptome of an organotypic model of human goblet cell metaplasia. We combined our data with previously published datasets from IL13-exposed in vitro and asthmatic in vivo human airway epithelial cells. The drug perturbation-response connectivity approach identified the heat shock protein 90 (HSP90) inhibitor geldanamycin as a candidate for reverting airway goblet cell metaplasia. We found that geldanamycin not only prevented but reverted IL13-induced goblet cell metaplasia. Geldanamycin did not induce goblet cell death, did not solely block mucin synthesis, and did not block IL13 receptor-proximal signaling. Moreover, the transcriptional effects of geldanamycin were absent in unstimulated cells and became evident only after stimulation with IL13. The predicted mechanism of action suggested that geldanamycin should also revert IL17-induced goblet cell metaplasia, a prediction confirmed by our data. Our findings suggest HSP90 activity may be required for persistence of goblet cell metaplasia driven by various mechanisms in chronic lung diseases.

2019-02-07 | GSE116927 | GEO

Foxa2 programs Th2-cell mediated innate immunity in the developing lung.

Project description:Deletion of the gene encoding Foxa2, a winged helix transcription factor selectively expressed in respiratory epithelial cells, caused spontaneous pulmonary eosinophilic inflammation and goblet cell metaplasia. Loss of Foxa2 induced the recruitment and activation of myeloid dendritic cells (mDCs) and Th2 cells in the lung, and was associated with the increased production of T helper 2 (Th2) cytokines and chemokines. mRNA microarray analysis demonstrated that deletion of Foxa2 induced the expression of a number of mRNAs regulating pulmonary dendritic cell activation, Th2 mediated inflammation, and goblet cell differentiation. The spontaneous pulmonary inflammation and goblet cell metaplasia caused by loss of Foxa2 was inhibited by treatment of newborn Foxa2∆/∆ mice with monoclonal IL-4Ralpha antibody. Expression of Foxa2 in non-ciliated secretory cells (Clara cells) in vivo inhibited goblet cell differentiation induced by pulmonary allergen exposure. The respiratory epithelium plays a central role in the regulation of Th2-mediated inflammation and innate immunity in the developing lung in a process regulated by Foxa2.

2010-02-25 | GSE19204 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data