Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells
Abstract 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, while iAT2s are primarily cultured in three-dimensional (3D) Matrigel, a matrix derived from cancerous mouse...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-37685-x |
| _version_ | 1797769568510279680 |
|---|---|
| author | Evan T. Hoffman Juan J. Uriarte Franziska E. Uhl Korin Eckstrom Alicia E. Tanneberger Chloe Becker Chloe Moulin Loredana Asarian Laertis Ikonomou Darrell N. Kotton Daniel J. Weiss |
| author_facet | Evan T. Hoffman Juan J. Uriarte Franziska E. Uhl Korin Eckstrom Alicia E. Tanneberger Chloe Becker Chloe Moulin Loredana Asarian Laertis Ikonomou Darrell N. Kotton Daniel J. Weiss |
| author_sort | Evan T. Hoffman |
| collection | DOAJ |
| description | Abstract 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, while iAT2s are primarily cultured in three-dimensional (3D) Matrigel, a matrix derived from cancerous mouse tissue, it is unclear how a physiologically relevant matrix will impact iAT2s phenotype. As extracellular matrix (ECM) is recognized as a vital component in directing cellular function and differentiation, we sought to derive hydrogels from decellularized human lung alveolar-enriched ECM (aECM) to provide an ex vivo model to characterize the role of physiologically relevant ECM on iAT2 phenotype. 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. |
| first_indexed | 2024-03-12T21:10:57Z |
| format | Article |
| id | doaj.art-628638ae4cf24318bc108d6cfcbea6a3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T21:10:57Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-628638ae4cf24318bc108d6cfcbea6a32023-07-30T11:11:25ZengNature PortfolioScientific Reports2045-23222023-07-0113111610.1038/s41598-023-37685-xHuman alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cellsEvan T. Hoffman0Juan J. Uriarte1Franziska E. Uhl2Korin Eckstrom3Alicia E. Tanneberger4Chloe Becker5Chloe Moulin6Loredana Asarian7Laertis Ikonomou8Darrell N. Kotton9Daniel J. Weiss10Department of Medicine, Larner College of Medicine, University of VermontDepartment of Physiology, College of Medicine, University of KentuckyDepartment of Experimental Medical Science, Lund UniversityDepartment of Microbiology and Molecular Genetics, Larner College of Medicine, University of VermontDepartment of Medicine, Larner College of Medicine, University of VermontDepartment of Medicine, Larner College of Medicine, University of VermontDepartment of Medicine, Larner College of Medicine, University of VermontDepartment of Medicine, Larner College of Medicine, University of VermontDepartment of Oral Biology, University of Buffalo, The State University of New YorkCenter for Regenerative Medicine, Boston University and Boston Medical CenterDepartment of Medicine, Larner College of Medicine, University of VermontAbstract 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, while iAT2s are primarily cultured in three-dimensional (3D) Matrigel, a matrix derived from cancerous mouse tissue, it is unclear how a physiologically relevant matrix will impact iAT2s phenotype. As extracellular matrix (ECM) is recognized as a vital component in directing cellular function and differentiation, we sought to derive hydrogels from decellularized human lung alveolar-enriched ECM (aECM) to provide an ex vivo model to characterize the role of physiologically relevant ECM on iAT2 phenotype. 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.https://doi.org/10.1038/s41598-023-37685-x |
| spellingShingle | Evan T. Hoffman Juan J. Uriarte Franziska E. Uhl Korin Eckstrom Alicia E. Tanneberger Chloe Becker Chloe Moulin Loredana Asarian Laertis Ikonomou Darrell N. Kotton Daniel J. Weiss Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells Scientific Reports |
| title | Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells |
| title_full | Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells |
| title_fullStr | Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells |
| title_full_unstemmed | Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells |
| title_short | Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells |
| title_sort | human alveolar hydrogels promote morphological and transcriptional differentiation in ipsc derived alveolar type 2 epithelial cells |
| url | https://doi.org/10.1038/s41598-023-37685-x |
| work_keys_str_mv | AT evanthoffman humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT juanjuriarte humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT franziskaeuhl humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT korineckstrom humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT aliciaetanneberger humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT chloebecker humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT chloemoulin humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT loredanaasarian humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT laertisikonomou humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT darrellnkotton humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells AT danieljweiss humanalveolarhydrogelspromotemorphologicalandtranscriptionaldifferentiationinipscderivedalveolartype2epithelialcells |