Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A longitudinal atlas of post-viral lung regeneration reveals persistent injury-associated cell states

ABSTRACT: Functional regeneration of the lung’s gas exchange surface following injury requires the coordination of a complex series of cell behaviors within the alveolar niche. Using a multi-modal approach, we have mapped the temporal sequencing of mouse lung regeneration after acute viral injury, demonstrating that this response is asynchronously phased across different cellular compartments. This longitudinal atlas of regeneration has produced a catalogue of new cell states that reflect transient and persistent transcriptional alterations in daughter cells as they transit across axes of differentiation. These new cell states include an injury-induced capillary endothelial cell (iCAP) that arises after injury, persists indefinitely, and shares transcriptional hallmarks with both developing lung endothelium and the endothelial aberrations found in degenerative human lung diseases. This comprehensive atlas of lung regeneration provides a foundational resource to understand the complexity of the cellular and molecular responses to injury, reveals the critical importance of capillary endothelium in maintaining and rebuilding the alveolar niche after injury, and correlates these responses to those found in development and human lung diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE262927 | GEO | 2024/12/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE262927_CellMetaData.csv.gz	Csv
	GSE262927_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 4 of 4

Similar Datasets

ATF3 promotes endothelial cell response to acute lung injury

Project description:Following acute injury, the capillary vascular bed in the lung must be repaired to reestablish gas exchange between pulmonary endothelial cells (ECs) lining these vessels and the alveolar epithelium. However, the factors that control EC stress response and drive regeneration of pulmonary capillaries remain incompletely understood. Viral infections such as influenza and COVID-19 may indirectly damage lung vasculature through loss of epithelial gas exchange partners or through signaling from infiltrating immune cells. To prevent excessive tissue damage and to renew the endothelium, ECs must both withstand cellular stress and proliferate after injury. Here, we show that the transcription factor and immediate early gene Atf3 is essential for both responses in the mouse lung after influenza infection. Atf3 expression defines a subpopulation of capillary ECs enriched in genes involved in cellular response to stress, angiogenesis, and vascular development. Endothelial loss of ATF3 results in defective alveolar regeneration: in the absence of ATF3, ECs exhibit increased apoptosis and decreased proliferation, resulting in an emphysema-like phenotype with enlarged alveolar airspaces lined with regions of lost vasculature. These data implicate ATF3 as an essential component of the vascular response to acute lung injury that is required for successful lung regeneration.

2023-05-19 | GSE213475 | GEO

Mapping pulmonary endothelial cell heterogeneity at homeostasis and during tissue regeneration

Project description:Pulmonary endothelial cells are an essential component of the lung alveolus, where they assist in integrating this niche with the cardiovascular system to perform gas exchange with the external environment. Despite its importance, the extent and function of endothelial cell heterogeneity within the lung remains incompletely understood. Using single-cell analytics, we show that multiple vascular endothelial cell populations exist in the mouse lung, including macrovascular endothelium (maECs), microvascular endothelium (miECs), and a new population we have termed regulator endothelium (RECs). RECs express a unique gene signature including elevated expression of Cd34 (Cd34high), Vegfr2 (Kdr), Ednrb, and Car4. The location of RECs within the lung is similar to other miECs at homeostasis, but they appear to preferentially invest regions of regenerating lung tissue after acute lung injury. Receptor-ligand analysis indicates that RECs are primed to receive reparative signals from alveolar type I cells through Vegfa-Vegfr2. Interestingly, influenza infection reveals the emergence of a highly proliferative endothelial cell population (PECs) that likely contributes to revascularization of the alveolar space after injury and may arise from Cd34low miECs. These studies map endothelial cell heterogeneity in the adult lung and characterize the preferential response of novel endothelial cell subpopulations required for proper tissue regeneration after acute lung injury.

2020-02-27 | GSE128944 | GEO

Temporal single-cell profiling of distinct mesenchymal, epithelial, endothelial, and immune cell lineages in the lung after injury

Project description:Upon severe injury to the lungs, a poorly understood multistep process results in either euplastic regeneration or dysplastic repair which leads to a loss of functional gas-exchanging alveolar tissue. We show that the dysplastic repair process consists of an injury-induced tissue niche (iTCH) containing Keratin 5+ epithelial cells and Pdgfra-derived Pdgfrb+ mesenchymal cells, which proliferate and transit across multiple cells states before localizing to dysplastic regions. Temporal and spatial single cell analysis reveals that Pdgfra-derived Pdgfrb+ cells communicate via Notch signaling to dysplastic keratinized epithelium. Inactivation of proliferation and Notch signaling in these Pdgfra+ progenitor mesenchymal cells prevents the establishment of iTCHs. Mesenchymal Notch signaling in iTCHs suppresses Wnt and Fgf signaling, whereas loss of Notch rewires alveolar signaling patterns to promote euplastic regeneration and restore functional gas exchange in the lung. iTCH presence and signaling patterns can be used to differentially phenotype fibrotic from degenerative chronic lung disease, with associated apposing flows of FGF and WNT signaling discriminating these disease states. These data reveal the emergence of an injury and disease associated niche in the lung, its regulation by mesenchymal Notch signaling, and the impact these cellular decisions have on discriminating the choice between dysplastic repair or euplastic regeneration.

2024-12-16 | GSE249931 | GEO

Inflammatory Signals induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration

Project description:Tissue regeneration is a multi-step process mediated by diverse cellular hierarchies and states that are also implicated in tissue dysfunction and pathogenesis. Here, we leveraged single-cell RNA sequencing in combination with in vivo lineage tracing and organoid models to finely map the trajectories of alveolar lineage cells during injury repair and lung regeneration. We identified a distinct AT2-lineage population, Damage-Associated Transient Progenitors (DATPs), that arises during alveolar regeneration. We found that interstitial macrophage-derived IL-1β primes a subset of AT2 cells expressing Il1r1 for conversion into DATPs via a HIF1α-mediated glycolysis pathway, which is required for mature AT1 cell differentiation. Importantly, chronic inflammation mediated by IL-1β prevents AT1 differentiation, leading to aberrant accumulation of DATPs and impaired alveolar regeneration. Together, this step-wise mapping to cell fate transitions shows how an inflammatory niche impairs alveolar regeneration by controlling stem cell fate and behavior.

2020-08-03 | GSE144598 | GEO

Inflammatory Signals induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration

2020-08-03 | GSE144468 | GEO

Inflammatory Signals induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration

2020-08-03 | GSE145031 | GEO

Hypoxia-inducible factor-2 (HIF2) regulates alveolar regeneration after repetitive injury

Project description:Idiopathic Pulmonary Fibrosis (IPF) is a progressive and often fatal chronic respiratory disease thought to result from repetitive injury and failed repair of the lung alveoli, and recent studies have identified a number of disease-emergent intermediate/transitional cell states in the IPF lung supporting this concept. In this study, we found that persistent activation of hypoxia-inducible factor (HIF)-signaling in airway-derived, repair-associated cell types/states is a hallmark of dysfunctional epithelial repair in the IPF lung epithelium and experimental models of recurrent lung epithelial injury. Disrupting Hif-signaling attenuated experimental lung fibrosis, reduced mucous-secretory cell polarization, and promoted functional alveolar regeneration following repetitive injury. Mouse and human organoid studies demonstrated that small-molecule-based HIF2 inhibition promoted alveolar epithelial cell proliferation and maturation while preventing the emergence of maladaptive intermediate/transitional states analogous to those in IPF. Together, these studies indicate that targeted HIF2-inhibition represents a novel and effective therapeutic strategy to promote functional lung regeneration, and could be readily translated into human studies of IPF and other chronic interstitial lung diseases with disease modifying effect.

2023-09-18 | GSE243252 | GEO

A grainyhead transcription factor Tfcp2l1 controls the timing for lung alveolar regeneration (RNA-Seq)

Project description:Alveolar epithelial type 2 (AT2) cells are facultative progenitor cells that drive adult alveolar regeneration after acute lung injury. Using transcriptomic analyses from in vivo mouse injury models, we define the role of Tfcp2l1 in regulating AT2 cell behavior during lung regeneration.

2023-09-12 | GSE204784 | GEO

A grainyhead transcription factor Tfcp2l1 controls the timing for lung alveolar regeneration (scRNA-Seq)

2023-09-12 | GSE204786 | GEO

Dynamic behavior and lineage plasticity of the pulmonary venous endothelium

Project description:Repair of the pulmonary vascular bed and the origin of new vasculature remains underexplored despite the critical necessity to meet oxygen demands after injury. Given their critical role in angiogenesis in other settings, we investigated the role of venous endothelial cells in endothelial regeneration after adult lung injury. Using single cell transcriptomics, we identified the norepinephrine transporter Slc6a2 as a marker of pulmonary venous endothelial cells and targeted that locus to generate a venous-specific, inducible Cre mouse line. Contributions of the venous endothelial cells to angiogenesis were examined during postnatal development, adult viral injury, and adult hyperoxia injury. Remarkably, we observed that venous endothelial cells proliferate into the adjacent capillary bed upon influenza injury and hyperoxia injury, but not during normal postnatal development. Imaging analysis demonstrated that venous endothelial cells exhibit the ability to proliferate and differentiate into general capillary and CAR4 expressing aerocyte capillary endothelial cells after infection, thus contributing to repair of the capillary plexus vital for gas exchange. Single cell transcriptomic analysis of Slc6a2 lineage traced cells confirmed these observations, with progeny exhibiting significant loss of venous identity and gain of capillary marker expression upon injury resolution. Our studies thus establish that venous endothelial cells exhibit demonstrable progenitor capacity upon respiratory viral injury and sterile injury, contributing to repair of the alveolar capillary bed responsible for pulmonary function.

2024-10-16 | GSE278220 | 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