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.
[doi:10.25345/C5M03Z70Z]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: aECM, hydrogels,iAT2
Principal Investigators: (in alphabetical order) |
Daniel J. Weiss, UVM, United States |
Submitting User: | bindeng |
Hoffman ET, Uriarte JJ, Uhl FE, Eckstrom K, Tanneberger AE, Becker C, Moulin C, Asarian L, Ikonomou L, Kotton DN, Weiss DJ.
Human alveolar hydrogels promote morphological and transcriptional differentiation in iPSC-derived alveolar type 2 epithelial cells.
Sci Rep. 2023 Jul 25;13(1):12057. Epub 2023 Jul 25.
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