Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.

ingentiumby ingentium

In Coronavirus Literature.

Publication date: Jul 17, 2026

Regional epithelial lineages of the human respiratory system reside within an extracellular matrix (ECM) whose mechanics vary along the airway-alveolar axis, yet how ECM stiffness directs epithelial fates remains unclear. Here, utilizing human pluripotent stem cell-derived lung organoids embedded in stiffness-tunable hydrogels as an in vitro model, we show ECM stiffness governs region-specific epithelial differentiation. Stepwise softening of ECM stiffness yields airway organoids with proximal-to-distal airway epithelial compositions and biomimetic physiological functions. During alveolar differentiation, increased stiffness promotes alveolar type 2 (AT2) and type 1 (AT1) maturation and drives AT2-to-AT1 transition. Furthermore, RNA sequencing reveals ECM stiffness regulates epithelial fates primarily through mechanotransduction pathways. Finally, these organoids reproduce the infection tropisms of SARS-CoV-2 variants. Together, this research elucidates ECM stiffness as a critical determinant of epithelial cell fate specification and region-specific lung organoid generation, which offers a valuable in vitro model for studying region-specific lung development, diseases pathogenesis, and drug screening.

Open Access PDF

Concepts Keywords
Airway
Alveolar
Derived
Differentiation
Directs
Ecm
Epithelial
Extracellular
Fates
Lung
Matrix
Organoids
Region
Specific
Stiffness

Semantics

Type Source Name
disease MESH AT1
disease MESH infection
drug DRUGBANK Troleandomycin
pathway REACTOME Reproduction
disease MESH included
disease MESH Allergy
disease MESH kPa
drug DRUGBANK Medical air
drug DRUGBANK Flunarizine
pathway REACTOME Integrin signaling
disease MESH sarcoma
drug DRUGBANK Gelatin
disease MESH LAP
drug DRUGBANK Water
drug DRUGBANK Collagenase clostridium histolyticum
drug DRUGBANK Phenobarbital
pathway REACTOME Apoptosis
drug DRUGBANK Vorinostat
pathway KEGG Peroxisome
disease MESH hypoxia
pathway REACTOME Metabolism
drug DRUGBANK Glycine
drug DRUGBANK Serine
drug DRUGBANK L-Threonine
drug DRUGBANK L-Tyrosine
drug DRUGBANK Colforsin
disease MESH FIS
drug DRUGBANK Tretamine
drug DRUGBANK Cyclic Adenosine Monophosphate
drug DRUGBANK Omega-3 fatty acids
pathway REACTOME Surfactant metabolism
drug DRUGBANK Tilmicosin
pathway KEGG Oxidative phosphorylation
disease MESH idiopathic pulmonary fibrosis
disease MESH fibrosis
disease MESH hpi
disease MESH Delta infection
disease MESH SARS CoV 2 infection
disease MESH lung diseases
drug DRUGBANK Hyaluronic acid
drug DRUGBANK Polyethylene glycol
pathway KEGG Focal adhesion
drug DRUGBANK Medroxyprogesterone acetate
drug DRUGBANK N-acetylsulfanilyl chloride
disease MESH injury
drug DRUGBANK Edetic Acid
disease MESH PBS
drug DRUGBANK Aspartame
disease MESH glass
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK 3-isobutyl-1-methyl-7H-xanthine
drug DRUGBANK Nitrogen
drug DRUGBANK Coenzyme M
disease MESH viral infection
disease MESH Image
disease MESH acc
disease MESH Bronchopulmonary Dysplasia
disease MESH pulmonary fibrosis
disease MESH Death
disease MESH Nonalcoholic Fatty Liver Disease
disease MESH Park
disease MESH lung injury
disease MESH Ito
disease MESH Respiratory Diseases
disease MESH metastasis
disease MESH influenza
drug DRUGBANK Pearl (hyriopsis cumingii)
drug DRUGBANK Pidolic Acid
disease MESH PCA
drug DRUGBANK Proline
disease MESH APC
pathway KEGG Hippo signaling pathway
pathway KEGG Tyrosine metabolism
pathway KEGG Wnt signaling pathway
pathway KEGG PPAR signaling pathway
pathway KEGG Hedgehog signaling pathway
pathway KEGG ErbB signaling pathway
pathway KEGG Viral replication

Original Article

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Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.

ingentiumby ingentium

In Coronavirus Literature.

Publication date: Jul 17, 2026

Regional epithelial lineages of the human respiratory system reside within an extracellular matrix (ECM) whose mechanics vary along the airway-alveolar axis, yet how ECM stiffness directs epithelial fates remains unclear. Here, utilizing human pluripotent stem cell-derived lung organoids embedded in stiffness-tunable hydrogels as an in vitro model, we show ECM stiffness governs region-specific epithelial differentiation. Stepwise softening of ECM stiffness yields airway organoids with proximal-to-distal airway epithelial compositions and biomimetic physiological functions. During alveolar differentiation, increased stiffness promotes alveolar type 2 (AT2) and type 1 (AT1) maturation and drives AT2-to-AT1 transition. Furthermore, RNA sequencing reveals ECM stiffness regulates epithelial fates primarily through mechanotransduction pathways. Finally, these organoids reproduce the infection tropisms of SARS-CoV-2 variants. Together, this research elucidates ECM stiffness as a critical determinant of epithelial cell fate specification and region-specific lung organoid generation, which offers a valuable in vitro model for studying region-specific lung development, diseases pathogenesis, and drug screening.

Open Access PDF

Concepts Keywords
Airway
Alveolar
Derived
Differentiation
Directs
Ecm
Epithelial
Extracellular
Fates
Lung
Matrix
Organoids
Region
Specific
Stiffness

Semantics

Type Source Name
disease MESH AT1
disease MESH infection
drug DRUGBANK Troleandomycin
pathway REACTOME Reproduction
disease MESH included
disease MESH Allergy
disease MESH kPa
drug DRUGBANK Medical air
drug DRUGBANK Flunarizine
pathway REACTOME Integrin signaling
disease MESH sarcoma
drug DRUGBANK Gelatin
disease MESH LAP
drug DRUGBANK Water
drug DRUGBANK Collagenase clostridium histolyticum
drug DRUGBANK Phenobarbital
pathway REACTOME Apoptosis
drug DRUGBANK Vorinostat
pathway KEGG Peroxisome
disease MESH hypoxia
pathway REACTOME Metabolism
drug DRUGBANK Glycine
drug DRUGBANK Serine
drug DRUGBANK L-Threonine
drug DRUGBANK L-Tyrosine
drug DRUGBANK Colforsin
disease MESH FIS
drug DRUGBANK Tretamine
drug DRUGBANK Cyclic Adenosine Monophosphate
drug DRUGBANK Omega-3 fatty acids
pathway REACTOME Surfactant metabolism
drug DRUGBANK Tilmicosin
pathway KEGG Oxidative phosphorylation
disease MESH idiopathic pulmonary fibrosis
disease MESH fibrosis
disease MESH hpi
disease MESH Delta infection
disease MESH SARS CoV 2 infection
disease MESH lung diseases
drug DRUGBANK Hyaluronic acid
drug DRUGBANK Polyethylene glycol
pathway KEGG Focal adhesion
drug DRUGBANK Medroxyprogesterone acetate
drug DRUGBANK N-acetylsulfanilyl chloride
disease MESH injury
drug DRUGBANK Edetic Acid
disease MESH PBS
drug DRUGBANK Aspartame
disease MESH glass
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK 3-isobutyl-1-methyl-7H-xanthine
drug DRUGBANK Nitrogen
drug DRUGBANK Coenzyme M
disease MESH viral infection
disease MESH Image
disease MESH acc
disease MESH Bronchopulmonary Dysplasia
disease MESH pulmonary fibrosis
disease MESH Death
disease MESH Nonalcoholic Fatty Liver Disease
disease MESH Park
disease MESH lung injury
disease MESH Ito
disease MESH Respiratory Diseases
disease MESH metastasis
disease MESH influenza
drug DRUGBANK Pearl (hyriopsis cumingii)
drug DRUGBANK Pidolic Acid
disease MESH PCA
drug DRUGBANK Proline
disease MESH APC
pathway KEGG Hippo signaling pathway
pathway KEGG Tyrosine metabolism
pathway KEGG Wnt signaling pathway
pathway KEGG PPAR signaling pathway
pathway KEGG Hedgehog signaling pathway
pathway KEGG ErbB signaling pathway
pathway KEGG Viral replication

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *

Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.

ingentiumby ingentium

In Coronavirus Literature.

Publication date: Jul 17, 2026

Regional epithelial lineages of the human respiratory system reside within an extracellular matrix (ECM) whose mechanics vary along the airway-alveolar axis, yet how ECM stiffness directs epithelial fates remains unclear. Here, utilizing human pluripotent stem cell-derived lung organoids embedded in stiffness-tunable hydrogels as an in vitro model, we show ECM stiffness governs region-specific epithelial differentiation. Stepwise softening of ECM stiffness yields airway organoids with proximal-to-distal airway epithelial compositions and biomimetic physiological functions. During alveolar differentiation, increased stiffness promotes alveolar type 2 (AT2) and type 1 (AT1) maturation and drives AT2-to-AT1 transition. Furthermore, RNA sequencing reveals ECM stiffness regulates epithelial fates primarily through mechanotransduction pathways. Finally, these organoids reproduce the infection tropisms of SARS-CoV-2 variants. Together, this research elucidates ECM stiffness as a critical determinant of epithelial cell fate specification and region-specific lung organoid generation, which offers a valuable in vitro model for studying region-specific lung development, diseases pathogenesis, and drug screening.

Open Access PDF

Concepts Keywords
Airway
Alveolar
Derived
Differentiation
Directs
Ecm
Epithelial
Extracellular
Fates
Lung
Matrix
Organoids
Region
Specific
Stiffness

Semantics

Type Source Name
disease MESH AT1
disease MESH infection
drug DRUGBANK Troleandomycin
pathway REACTOME Reproduction
disease MESH included
disease MESH Allergy
disease MESH kPa
drug DRUGBANK Medical air
drug DRUGBANK Flunarizine
pathway REACTOME Integrin signaling
disease MESH sarcoma
drug DRUGBANK Gelatin
disease MESH LAP
drug DRUGBANK Water
drug DRUGBANK Collagenase clostridium histolyticum
drug DRUGBANK Phenobarbital
pathway REACTOME Apoptosis
drug DRUGBANK Vorinostat
pathway KEGG Peroxisome
disease MESH hypoxia
pathway REACTOME Metabolism
drug DRUGBANK Glycine
drug DRUGBANK Serine
drug DRUGBANK L-Threonine
drug DRUGBANK L-Tyrosine
drug DRUGBANK Colforsin
disease MESH FIS
drug DRUGBANK Tretamine
drug DRUGBANK Cyclic Adenosine Monophosphate
drug DRUGBANK Omega-3 fatty acids
pathway REACTOME Surfactant metabolism
drug DRUGBANK Tilmicosin
pathway KEGG Oxidative phosphorylation
disease MESH idiopathic pulmonary fibrosis
disease MESH fibrosis
disease MESH hpi
disease MESH Delta infection
disease MESH SARS CoV 2 infection
disease MESH lung diseases
drug DRUGBANK Hyaluronic acid
drug DRUGBANK Polyethylene glycol
pathway KEGG Focal adhesion
drug DRUGBANK Medroxyprogesterone acetate
drug DRUGBANK N-acetylsulfanilyl chloride
disease MESH injury
drug DRUGBANK Edetic Acid
disease MESH PBS
drug DRUGBANK Aspartame
disease MESH glass
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK 3-isobutyl-1-methyl-7H-xanthine
drug DRUGBANK Nitrogen
drug DRUGBANK Coenzyme M
disease MESH viral infection
disease MESH Image
disease MESH acc
disease MESH Bronchopulmonary Dysplasia
disease MESH pulmonary fibrosis
disease MESH Death
disease MESH Nonalcoholic Fatty Liver Disease
disease MESH Park
disease MESH lung injury
disease MESH Ito
disease MESH Respiratory Diseases
disease MESH metastasis
disease MESH influenza
drug DRUGBANK Pearl (hyriopsis cumingii)
drug DRUGBANK Pidolic Acid
disease MESH PCA
drug DRUGBANK Proline
disease MESH APC
pathway KEGG Hippo signaling pathway
pathway KEGG Tyrosine metabolism
pathway KEGG Wnt signaling pathway
pathway KEGG PPAR signaling pathway
pathway KEGG Hedgehog signaling pathway
pathway KEGG ErbB signaling pathway
pathway KEGG Viral replication

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *