ECE2013 Symposia Novel technologies and inspiring ideas: From basic endocrine research to clinical practice (European Young Endocrine Scientists (EYES) Symposium) (3 abstracts)
Making a functional thyroid in a dish
Francesco Antonica 1 , Dominika Figini Kasprzyk 1 , Robert Opitz 1 , Michelina Iacovino 2 , Xiao-Hui Liao 3 , Alexandra Mihaela Dumitrescu 3 , Samuel Refetoff 3, , Kathelijne Peremans 5 , Mario Manto 6 , Michael Kyba 2 & Sabine Costagliola 1
1Institute of Interdisciplinary Research in Molecular Human Biology (IRIBHM), Université Libre de Bruxelles, 808 route de Lennik, 1070 Brussels, Belgium; 2Lillehei Heart Institute and Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; 3Department of Medicine, The University of Chicago, Chicago, Illinois, USA; 4Departments of Pediatrics and Genetics, The University of Chicago, Chicago, Illinois, USA; 5Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium; 6FNRS, ERASME, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium.
During the last decade induced overexpression of defined transcription factors has been shown to have a driving effect on the differentiation of embryonic stem cells (ESCs) into many specific cell types. Nevertheless, the generation of protocols promoting a coordinate self-assembly of differentiated cells into distinct morphological units with also functional properties reminiscent of organs and tissues in vivo are still very sparse. Recently, we have reported the generation of functional thyroid follicles generated from pluripotent stem cells. We show that a transient overexpression of the transcription factors NKX2.1 and PAX8, notably know to play a pivotal role during thyroid organogenesis, in addition to a subsequent treatment with TSH is sufficient to direct murine ESC differentiation into thyroid follicular cells (TFC) and promotes in vitro self-assembly of TFC into three-dimensional follicular structures. In addition to morphological evidences, cells differentiated by this protocol showed significant iodide organification activity, a second hallmark of thyroid tissue function. Importantly, athyroid mice grafted with mESC-derived thyroid follicles show normalization of plasma T4 levels with concomitant decrease of plasma TSH. Moreover, normalization of body temperature had been observed upon transplantation of thyroid follicles into athyroid mice. Our findings have demonstrated that mESCs can efficiently be differentiated into TFCs that can self-assembly into 3D functional units and finally transplanted in athyroid mice rescuing the hypothyroid state and triggering symptomatic recovery along with the normalization of plasma hormone concentrations. Moreover, the high efficiency of TFC differentiation and follicle morphogenesis in our system will provide an unprecedented opportunity for future studies to decipher regulatory mechanisms involved in embryonic thyroid development. Translating the methodology on human using hESC and iPSCs could give an important contribution in the understanding of the molecular mechanisms underlying congenital hypothyroidism and thyroid.
Volume 32
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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