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Generation of functional thyroid from embryonic stem cells

Author

Listed:
  • Francesco Antonica

    (Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Université Libre de Bruxelles)

  • Dominika Figini Kasprzyk

    (Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Université Libre de Bruxelles)

  • Robert Opitz

    (Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Université Libre de Bruxelles)

  • Michelina Iacovino

    (University of Minnesota)

  • Xiao-Hui Liao

    (The University of Chicago)

  • Alexandra Mihaela Dumitrescu

    (The University of Chicago)

  • Samuel Refetoff

    (The University of Chicago
    The University of Chicago)

  • Kathelijne Peremans

    (Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium)

  • Mario Manto

    (FNRS, ERASME, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium)

  • Michael Kyba

    (University of Minnesota)

  • Sabine Costagliola

    (Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Université Libre de Bruxelles)

Abstract

The primary function of the thyroid gland is to metabolize iodide by synthesizing thyroid hormones, which are critical regulators of growth, development and metabolism in almost all tissues. So far, research on thyroid morphogenesis has been missing an efficient stem-cell model system that allows for the in vitro recapitulation of the molecular and morphogenic events regulating thyroid follicular-cell differentiation and subsequent assembly into functional thyroid follicles. Here we report that a transient overexpression of the transcription factors NKX2-1 and PAX8 is sufficient to direct mouse embryonic stem-cell differentiation into thyroid follicular cells that organize into three-dimensional follicular structures when treated with thyrotropin. These in vitro-derived follicles showed appreciable iodide organification activity. Importantly, when grafted in vivo into athyroid mice, these follicles rescued thyroid hormone plasma levels and promoted subsequent symptomatic recovery. Thus, mouse embryonic stem cells can be induced to differentiate into thyroid follicular cells in vitro and generate functional thyroid tissue.

Suggested Citation

  • Francesco Antonica & Dominika Figini Kasprzyk & Robert Opitz & Michelina Iacovino & Xiao-Hui Liao & Alexandra Mihaela Dumitrescu & Samuel Refetoff & Kathelijne Peremans & Mario Manto & Michael Kyba & , 2012. "Generation of functional thyroid from embryonic stem cells," Nature, Nature, vol. 491(7422), pages 66-71, November.
    • Handle: RePEc:nat:nature:v:491:y:2012:i:7422:d:10.1038_nature11525
    DOI: 10.1038/nature11525
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    Cited by:

    1. Mírian Romitti & Adrien Tourneur & Barbara Faria da Fonseca & Gilles Doumont & Pierre Gillotay & Xiao-Hui Liao & Sema Elif Eski & Gaetan Simaeys & Laura Chomette & Helene Lasolle & Olivier Monestier &, 2022. "Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Teresa L. Rapp & Cole A. DeForest, 2023. "Tricolor visible wavelength-selective photodegradable hydrogel biomaterials," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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