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

Autor: Hoffman ET; Department of Medicine, Larner College of Medicine, University of Vermont, 149 Beaumont Avenue, Burlington, VT, 05405, USA., Uriarte JJ; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, 40506, USA., Uhl FE; Department of Experimental Medical Science, Lund University, Lund, Sweden.; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden., Eckstrom K; Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA., Tanneberger AE; Department of Medicine, Larner College of Medicine, University of Vermont, 149 Beaumont Avenue, Burlington, VT, 05405, USA., Becker C; Department of Medicine, Larner College of Medicine, University of Vermont, 149 Beaumont Avenue, Burlington, VT, 05405, USA., Moulin C; Department of Medicine, Larner College of Medicine, University of Vermont, 149 Beaumont Avenue, Burlington, VT, 05405, USA., Asarian L; Department of Medicine, Larner College of Medicine, University of Vermont, 149 Beaumont Avenue, Burlington, VT, 05405, USA., Ikonomou L; Department of Oral Biology, University of Buffalo, The State University of New York, Buffalo, NY, 14260, USA.; Cell, Gene and Tissue Engineering Center, University at Buffalo, The State University of New York, Buffalo, NY, USA., Kotton DN; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA, 02118, USA., Weiss DJ; Department of Medicine, Larner College of Medicine, University of Vermont, 149 Beaumont Avenue, Burlington, VT, 05405, USA. daniel.weiss@med.uvm.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Jul 25; Vol. 13 (1), pp. 12057. Date of Electronic Publication: 2023 Jul 25.
DOI: 10.1038/s41598-023-37685-x
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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