Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Modeling of spontaneous pulmonary fibrosis via cellular senescence in type 2 alveolar epithelial cells derived from human iPSCs [epithelial]

ABSTRACT: Telomere dysfunction in type II alveolar epithelial (AT2) cells causes pulmonary fibrosis in a subset of patients. TRF2 is a key component of the shelterin complex (SC) which prevents abnormally shortened and uncapped telomeres and genetic variants of SC were reported in some familial cases of IPF. We conceived that in vitro senescence model of AT2 cells derived from human induced pluripotent stem cells (iPSCs) would be beneficial for elucidating the mechanism of IPF progression. Then we generated an iPSC line using a doxycycline (dox) -inducible lentiviral vector encoding the dominant negative variant of TRF2 (TRF2DN). We next differentiated this iPSC line into AT2 (iAT2) cells and expressed TRF2DN protein in a dox-inducible manner. Alveolar organoids consisting of TRF2DN-expressing iAT2 cells and human fetal lung fibroblasts showed contraction of the organoid matrices

ORGANISM(S): Homo sapiens

PROVIDER: GSE289679 | GEO | 2026/02/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE289679_TRF2_FDAO_Epithelial_COUNT.txt.gz	Txt

Items per page:

1 - 2 of 2

Similar Datasets

Modeling of spontaneous pulmonary fibrosis via cellular senescence in type 2 alveolar epithelial cells derived from human iPSCs [HFLF]

Project description:Telomere dysfunction in type II alveolar epithelial (AT2) cells causes pulmonary fibrosis in a subset of patients. TRF2 is a key component of the shelterin complex (SC) which prevents abnormally shortened and uncapped telomeres and genetic variants of SC were reported in some familial cases of IPF. We conceived that in vitro senescence model of AT2 cells derived from human induced pluripotent stem cells (iPSCs) would be beneficial for elucidating the mechanism of IPF progression. Then we generated an iPSC line using a doxycycline (dox) -inducible lentiviral vector encoding the dominant negative variant of TRF2 (TRF2DN). We next differentiated this iPSC line into AT2 (iAT2) cells and expressed TRF2DN protein in a dox-inducible manner. Alveolar organoids consisting of TRF2DN-expressing iAT2 cells and human fetal lung fibroblasts showed contraction of the organoid matrices

2026-02-18 | GSE289682 | GEO

Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells

Project description:To investigate the role of alveolar extracellular matrix (aECM) hydrogels on iPSC-derived alveolar type 2 epithelial cell (iAT2) morphological and transcriptional differentiation

2023-03-21 | GSE227546 | GEO

Impaired AMPK Control of Alveolar Epithelial Cell Metabolism Promotes Pulmonary Fibrosis

Project description:Alveolar epithelial type II (AT2) cell dysfunction is implicated in the pathogenesis of familial and sporadic idiopathic pulmonary fibrosis (IPF). We previously demonstrated that expression of an AT2 cell exclusive disease-associated protein isoform (SP-CI73T) in murine and patient-specific induced pluripotent stem cell (iPSC)-derived AT2 cells leads to a block in late macroautophagy and promotes time-dependent mitochondrial impairments; however, how a metabolically dysfunctional AT2 cell results in fibrosis remains elusive. Here, using murine and human iPSC-derived AT2 cell models expressing SP-CI73T, we characterize the molecular mechanisms governing alterations in AT2 cell metabolism that lead to increased glycolysis, decreased mitochondrial biogenesis, disrupted fatty acid oxidation, accumulation of impaired mitochondria, and diminished AT2 cell progenitor capacity manifesting as reduced AT2 self-renewal and accumulation of transitional epithelial cells. We identify deficient AMP-kinase signaling as a key upstream driver of AT2 cell dysfunction and demonstrate that targeting this druggable signaling hub can rescue the aberrant AT2 cell metabolic phenotype and mitigate lung fibrosis in vivo.

2025-06-24 | GSE296513 | GEO

Transcriptional profiling of short telomere iPS derived sorted SFTPC+ iAT2 cells

Project description:Dyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age_Related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human iPSC-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Cultured DC mutant iAT2 cells accumulate shortened, uncapped telomeres and manifest defects in the growth of alveolospheres, hallmarks of senescence, and apparent defects in Wnt signaling. The GSK3 inhibitor, CHIR99021, which mimics the output of canonical Wnt signaling, enhances telomerase activity and rescues the defects. These findings support further investigation of Wnt agonists as potential therapies for DC related pathologies.

2021-05-07 | GSE160871 | GEO

Epithelial Yap/Taz are required for functional alveolar regeneration following acute lung injury

Project description:A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrated that Yap and Taz are normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2 to AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to a LPS injury prevented AT1 cell regeneration, led to intra-alveolar collagen deposition, and resulted in persistent innate inflammation. Together these findings established that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling.

2023-11-15 | GSE243135 | GEO

Single Cell RNA-Sequencing Identifies Diverse Roles of Epithelial Cells in Idiopathic Pulmonary Fibrosis

Project description:Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease causing alveolar remodeling, inflammation, and fibrosis. We utilized single cell RNA-sequencing (scRNA-Seq) to identify epithelial cell types and associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis of epithelial cells from normal human lung defined gene expression patterns associated with highly differentiated alveolar type 2 (AT2) cells, indicated by enrichment of RNAs critical for surfactant homeostasis. In contrast, scRNA-seq of IPF cells identified three distinct subsets of epithelial cell types with characteristics of conducting airway basal and goblet cells and, an additional atypical "transitional" cell that contribute to pathological processes in IPF. Individual IPF cells frequently co-expressed alveolar AT1, AT2, and conducting airway selective markers, demonstrating "indeterminate" states of differentiation not seen in normal lung development. Pathway analysis predicted aberrant activation of canonical signaling via TGF-ß, HIPPO/YAP, P53, and AKT-PI3 Kinase. Immunofluorescence confocal microscopy identified the disruption of alveolar structure and loss of the normal proximal-peripheral differentiation of pulmonary epithelial cells. Single cell transcriptomic analyses of respiratory epithelial cells identified loss of normal epithelial cell identities and unique contributions of epithelial cells to the pathogenesis of IPF. Present scRNA-seq transcriptomic analysis of normal and IPF respiratory epithelial cells provides a rich data source to further explore lung health and disease.

2017-02-06 | GSE94555 | GEO

Single Cell RNA-Sequencing Identifies Diverse Roles of Epithelial Cells in Idiopathic Pulmonary Fibrosis

2016-12-08 | GSE86618 | GEO

Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells

Project description:Alveolar type 2 epithelial cells (AT2s) derived from human induced pluripotent stem cells (iAT2s) have rapidly contributed to our understanding of AT2 function and disease. However, as iAT2s are primarily cultured in three-dimensional (3D) Matrigel, a matrix derived from cancerous mouse tissue, it is unclear the impact a physiologically relevant matrix will have on iAT2s. Herein, we derive hydrogels from decellularized human lung alveolar-enriched extracellular matrix (aECM) to provide a relevant ex vivo model for the 3D culture of iAT2s. We demonstrate aECM hydrogels retain critical in situ ECM components, including structural and basement membrane proteins. While aECM hydrogels facilitate iAT2 proliferation and alveolosphere formation, a subset of iAT2s rapidly change morphology to thin and elongated ring-like cells. This morphological change correlates with upregulation of recently described iAT2-derived transitional cell state genetic markers. As such, we demonstrate a potentially underappreciated role of physiologically relevant aECM in iAT2 differentiation.

2023-03-10 | MSV000091470 | MassIVE

Fgf10-Fgfr2b signaling generates basal cells and drives alveolar epithelial regeneration by bronchial epithelial stem cells after lung injury

Project description:Idiopathic pulmonary fibrosis (IPF) is a common form of interstitial lung disease (ILD) resulting in alveolar remodeling and progressive loss of pulmonary function due to chronic alveolar injury and failure to regenerate the respiratory epithelium. Histologically, fibrotic lesions and honeycomb structures expressing atypical proximal airway epithelial markers replace alveolar structures, the latter normally lined by alveolar type 1 (AT1) and AT2 cells. Bronchial epithelial stem cells (BESCs) can give rise to AT2 and AT1 cells or honeycomb cysts following bleomycin-mediated lung injury. However, little is known about what controls this binary decision or whether this decision can be reversed. Here we report that inactivation of Fgfr2b in BESCs impairs their contribution to both alveolar epithelial regeneration and honeycomb cysts after bleomycin injury. By contrast overexpression of Fgf10 in BESCs enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts.

2019-03-30 | GSE129079 | GEO

Integrated multiomic analysis identifies TRIP13 as a mediator of alveolar epithelial type II cell dysfunction in idiopathic pulmonary fibrosis

Project description:Idiopathic pulmonary fibrosis (IPF) is a lethal progressive lung disease urgently needing new therapies. Current treatments only delay disease progression, leaving lung transplant as the sole remaining option. Recent studies support a model whereby IPF arises because alveolar epithelial type II (AT2) cells, which normally mediate distal lung regeneration, acquire airway and/or mesenchymal characteristics, preventing proper repair. Mechanisms driving this abnormal differentiation remain unclear. We performed integrated transcriptomic and epigenomic analysis of purified AT2 cells which revealed genome-wide alterations in IPF lungs. The most prominent epigenetic alteration was activation of an enhancer in thyroid receptor interactor 13 (TRIP13), coinciding with TRIP13 upregulation. TRIP13 is broadly implicated in epithelial-mesenchymal plasticity and transforming growth factor-beta signaling. In cultured human AT2 cells and lung slices, small molecule TRIP inhibitor DCZ0415 prevented acquisition of the mesenchymal gene signature characteristic of IPF, suggesting TRIP13 inhibition as a potential therapeutic approach to fibrotic disease.

2024-11-18 | GSE245965 | 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