iPSC-derived mesenchymal cells that support alveolar organoid development.
Cell Rep Methods
; 2(10): 100314, 2022 10 24.
Article
in En
| MEDLINE
| ID: mdl-36313800
ABSTRACT
Mesenchymal cells are necessary for organ development. In the lung, distal tip fibroblasts contribute to alveolar and airway epithelial cell differentiation and homeostasis. Here, we report a method for generating human induced pluripotent stem cell (iPSC)-derived mesenchymal cells (iMESs) that can induce human iPSC-derived alveolar and airway epithelial lineages in organoids via epithelial-mesenchymal interaction, without the use of allogenic fetal lung fibroblasts. Through a transcriptome comparison of dermal and lung fibroblasts with their corresponding reprogrammed iPSC-derived iMESs, we found that iMESs had features of lung mesenchyme with the potential to induce alveolar type 2 (AT2) cells. Particularly, RSPO2 and RSPO3 expressed in iMESs directly contributed to AT2 cell induction during organoid formation. We demonstrated that the total iPSC-derived alveolar organoids were useful for characterizing responses to the influenza A (H1N1) virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, demonstrating their utility for disease modeling.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Influenza A Virus, H1N1 Subtype
/
Induced Pluripotent Stem Cells
/
COVID-19
Limits:
Humans
Language:
En
Journal:
Cell Rep Methods
Year:
2022
Document type:
Article
Affiliation country: