title: Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells.
abstract: Two populations of Nkx2-1(+) progenitors in the developing foregut endoderm give rise to the entire postnatal lung and thyroid epithelium, but little is known about these cells because they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGFβ and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling, can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1(GFP) knockin reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development.
authors.affiliation: Boston University Pulmonary Center, Boston University School of Medicine, MA 02118, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Longmire
authors.forename: Laertis
authors.initials: L
authors.lastname: Ikonomou
authors.forename: Finn
authors.initials: F
authors.lastname: Hawkins
authors.forename: Constantina
authors.initials: C
authors.lastname: Christodoulou
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Cao
authors.forename: J C
authors.initials: JC
authors.lastname: Jean
authors.forename: Letty W
authors.initials: LW
authors.lastname: Kwok
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mou
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Rajagopal
authors.forename: Steven S
authors.initials: SS
authors.lastname: Shen
authors.forename: Anne A
authors.initials: AA
authors.lastname: Dowton
authors.forename: Maria
authors.initials: M
authors.lastname: Serra
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
authors.forename: Michael D
authors.initials: MD
authors.lastname: Green
authors.forename: Hans-Willem
authors.initials: HW
authors.lastname: Snoeck
authors.forename: Maria I
authors.initials: MI
authors.lastname: Ramirez
authors.forename: Darrell N
authors.initials: DN
authors.lastname: Kotton
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002469:Cell Separation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000502:physiology; D013961:Thyroid Gland / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D054457:Tissue Scaffolds
chemical_list: D019485:Bone Morphogenetic Proteins; D005346:Fibroblast Growth Factors