title: Acellular lung scaffolds direct differentiation of endoderm to functional airway epithelial cells: requirement of matrix-bound HS proteoglycans.
abstract: Efficient differentiation of pluripotent cells to proximal and distal lung epithelial cell populations remains a challenging task. The 3D extracellular matrix (ECM) scaffold is a key component that regulates the interaction of secreted factors with cells during development by often binding to and limiting their diffusion within local gradients. Here we examined the role of the lung ECM in differentiation of pluripotent cells in vitro and demonstrate the robust inductive capacity of the native lung matrix alone. Extended culture of stem cell-derived definitive endoderm on decellularized lung scaffolds in defined, serum-free medium resulted in differentiation into mature airway epithelia, complete with ciliated cells, club cells, and basal cells with morphological and functional similarities to native airways. Heparitinase I, but not chondroitinase ABC, treatment of scaffolds revealed that the differentiation achieved is dependent on heparan sulfate proteoglycans and its bound factors remaining on decellularized scaffolds.
authors: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada.
authors: Sharareh
authors: S
authors: Shojaie
authors: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors: Leonardo
authors: L
authors: Ermini
authors: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors: Cameron
authors: C
authors: Ackerley
authors: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors: Jinxia
authors: J
authors: Wang
authors: Program in Molecular Structure and Function, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors: Stephanie
authors: S
authors: Chin
authors: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors: Behzad
authors: B
authors: Yeganeh
authors: Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors: Mélanie
authors: M
authors: Bilodeau
authors: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
authors: Manpreet
authors: M
authors: Sambi
authors: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
authors: Ian
authors: I
authors: Rogers
authors: Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors: Janet
authors: J
authors: Rossant
authors: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada; Program in Molecular Structure and Function, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors: Christine E
authors: CE
authors: Bear
authors: Program in Physiology and Experimental Medicine, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada. Electronic address: martin.post@sickkids.ca.
authors: Martin
authors: M
authors: Post
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004707:Endoderm / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D019812:Heparan Sulfate Proteoglycans; D009687:Nuclear Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator