title: Regeneration of Thyroid Function by Transplantation of Differentiated Pluripotent Stem Cells.
abstract: Differentiation of functional thyroid epithelia from pluripotent stem cells (PSCs) holds the potential for application in regenerative medicine. However, progress toward this goal is hampered by incomplete understanding of the signaling pathways needed for directed differentiation without forced overexpression of exogenous transgenes. Here we use mouse PSCs to identify key conserved roles for BMP and FGF signaling in regulating thyroid lineage specification from foregut endoderm in mouse and Xenopus. Thyroid progenitors derived from mouse PSCs can be matured into thyroid follicular organoids that provide functional secretion of thyroid hormones in vivo and rescue hypothyroid mice after transplantation. Moreover, by stimulating the same pathways, we were also able to derive human thyroid progenitors from normal and disease-specific iPSCs generated from patients with hypothyroidism resulting from NKX2-1 haploinsufficiency. Our studies have therefore uncovered the regulatory mechanisms that underlie early thyroid organogenesis and provide a significant step toward cell-based regenerative therapy for hypothyroidism.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Anita A
authors.initials: AA
authors.lastname: Kurmann
authors.affiliation: Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Serra
authors.affiliation: Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Finn
authors.initials: F
authors.lastname: Hawkins
authors.affiliation: Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rankin
authors.affiliation: Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Munemasa
authors.initials: M
authors.lastname: Mori
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Astapova
authors.affiliation: Longwood Small Animal Imaging Facility, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Soumya
authors.initials: S
authors.lastname: Ullas
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
authors.forename: Sui
authors.initials: S
authors.lastname: Lin
authors.affiliation: Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bilodeau
authors.affiliation: Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.affiliation: Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Jyh C
authors.initials: JC
authors.lastname: Jean
authors.affiliation: Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Laertis
authors.initials: L
authors.lastname: Ikonomou
authors.affiliation: Breathing Institute at the Children's Hospital Colorado and Section of Pediatric Pulmonary Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Deterding
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Shannon
authors.affiliation: Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Zorn
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Electronic address: thollenb@bidmc.harvard.edu.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hollenberg
authors.affiliation: Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: dkotton@bu.edu.
authors.forename: Darrell N
authors.initials: DN
authors.lastname: Kotton
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation*; D012038:Regeneration; D013961:Thyroid Gland / Q000166:cytology* / Q000502:physiology*; D014981:Xenopus