Human Alveolar Hydrogels Promote Morphological and Transcriptional Differentiation in IPSC-derived Alveolar Type 2 Epithelial Cells

Overview

Journal Sci Rep

Specialty Science

Date 2023 Jul 25

PMID 37491483

Authors

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

Affiliations

Soon will be listed here.

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.

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