Generation of organized anterior foregut epithelia from pluripotent stem cells using small molecules. 2013

Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.

Anterior foregut endoderm (AFE) gives rise to therapeutically relevant cell types in tissues such as the esophagus, salivary glands, lung, thymus, parathyroid and thyroid. Despite its importance, reports describing the generation of AFE from pluripotent stem cells (PSCs) by directed differentiation have mainly focused on the Nkx2.1(+) lung and thyroid lineages. Here, we describe a novel protocol to derive a subdomain of AFE, identified by expression of Pax9, from PSCs using small molecules and defined media conditions. We generated a reporter PSC line for isolation and characterization of Pax9(+) AFE cells, which when transplanted in vivo, can form several distinct complex AFE-derived epithelia, including mucosal glands and stratified squamous epithelium. Finally, we show that the directed differentiation protocol can be used to generate AFE from human PSCs. Thus, this work both broadens the range of PSC-derived AFE tissues and creates a platform enabling the study of AFE disorders.

UI MeSH Term Description Entries
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003470 Culture Media Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN. Media, Culture
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074482 Thyroid Nuclear Factor 1 A homeobox protein and transcription factor that localizes to the cell nucleus where it activates expression of thyroid specific genes such as THYROGLOBULIN and the THYROTROPIN RECEPTOR. It is critical for maintaining thyroid tissue in a differentiated state and also plays a role in lung development. Mutations in the NKX2-1 gene are associated with CHOREA, BENIGN HEREDITARY. Homeobox Protein Nkx-2.1,NK2 Homeobox 1 Protein,TITF-1 Protein,TITF1 Protein,TTF-1 Thyroid Nuclear Factor,Thyroid Transcription Factor 1,Thyroid-Specific Enhancer-Binding Protein,Enhancer-Binding Protein, Thyroid-Specific,Homeobox Protein Nkx 2.1,Nkx-2.1, Homeobox Protein,TITF 1 Protein,TTF 1 Thyroid Nuclear Factor,Thyroid Specific Enhancer Binding Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
March 2011, Nature biotechnology,
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
January 2013, Stem cell reports,
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
January 2010, Methods in molecular biology (Clifton, N.J.),
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
September 2021, Stem cell reports,
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
January 2018, Differentiation; research in biological diversity,
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
September 2010, Hepatology (Baltimore, Md.),
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
January 2015, Biomaterials,
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
April 2024, International journal of molecular sciences,
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
April 2014, Proceedings of the National Academy of Sciences of the United States of America,
Nicola A Kearns, and Ryan M J Genga, and Michael Ziller, and Kristina Kapinas, and Heiko Peters, and Michael A Brehm, and Alexander Meissner, and René Maehr
August 2013, Nature,
Copied contents to your clipboard!