Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

被引：49

作者：

Ogundipe, Vivian M. L. ^{[1
,3
]}

Groen, Andries H. ^{[1
,2
]}

Hosper, Nynke ^{[1
,3
]}

Nagle, Peter W. K. ^{[1
,2
,3
,7
]}

Hess, Julia ^{[5
,6
]}

Faber, Hette ^{[1
,3
]}

Jellema, Anne L. ^{[1
]}

Baanstra, Mirjam ^{[1
,3
]}

Links, Thera P. ^{[4
]}

Unger, Kristian ^{[5
,6
]}

Plukker, John T. M. ^{[2
]}

Coppes, Rob P. ^{[1
,3
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Biomed Sci Cells & Syst, Sect Mol Cell Biol, NL-9713 GZ Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Surg Oncol, NL-9713 GZ Groningen, Netherlands

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Radiat Oncol, NL-9713 GZ Groningen, Netherlands

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, NL-9713 GZ Groningen, Netherlands

[5] Helmholtz Zentrum Munchen, Res Unit Radiat Cytogenet, German Res Ctr Environm Hlth GmbH, D-85764 Neuherberg, Germany

[6] Ludwig Maximilians Univ Munchen, Dept Radiat Oncol, Univ Hosp, D-81377 Munich, Germany

[7] Univ Edinburgh, Canc Res UK Edinburgh Ctr, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

来源：

STEM CELL REPORTS | 2021年 / 16卷 / 04期

关键词：

EMBRYONIC STEM-CELLS; HORMONE REPLACEMENT; LONG-TERM; IN-VITRO; MOUSE; EXPRESSION; EXPANSION; STIMULATION; SYSTEM; GENES;

D O I：

10.1016/j.stemcr.2021.02.011

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Total thyroidectomy as part of thyroid cancer treatment results in hypothyroidism requiring lifelong daily thyroid hormone replacement. Unbalanced hormone levels result in persistent complaints such as fatigue, constipation, and weight increase. Therefore, we aimed to investigate a patient-derived thyroid organoid model with the potential to regenerate the thyroid gland. Murine and human thyroidderived cells were cultured as organoids capable of self-renewal and which expressed proliferation and putative stem cell and thyroid characteristics, without a change in the expression of thyroid tumor-related genes. These organoids formed thyroid-tissue-resembling structures in culture. (Xeno-)transplantation of 600,000 dispersed organoid cells underneath the kidney capsule of a hypothyroid mouse model resulted in the generation of hormone-producing thyroid-resembling follicles. This study provides evidence that thyroid-lineagespecific cells can form organoids that are able to self-renew and differentiate into functional thyroid tissue. Subsequent (xeno-)transplantation of these thyroid organoids demonstrates a proof of principle for functional miniature gland formation.

引用

页码：913 / 925

页数：13

共 56 条

[1] Integrated Genomic Characterization of Papillary Thyroid Carcinoma [J].

Agrawal, Nishant ;

Akbani, Rehan ;

Aksoy, B. Arman ;

Ally, Adrian ;

Arachchi, Harindra ;

Asa, Sylvia L. ;

Auman, J. Todd ;

Balasundaram, Miruna ;

Balu, Saianand ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bishop, Justin A. ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Bootwalla, Moiz S. ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brookens, Robin ;

Brooks, Denise ;

Bryant, Robert ;

Buda, Elizabeth ;

Butterfield, Yaron S. N. ;

Carling, Tobias ;

Carlsen, Rebecca ;

Carter, Scott L. ;

Carty, Sally E. ;

Chan, Timothy A. ;

Chen, Amy Y. ;

Cherniack, Andrew D. ;

Cheung, Dorothy ;

Chin, Lynda ;

Cho, Juok ;

Chu, Andy ;

Chuah, Eric ;

Cibulskis, Kristian ;

Ciriello, Giovanni ;

Clarke, Amanda ;

Clayman, Gary L. ;

Cope, Leslie ;

Copland, John A. ;

Covington, Kyle ;

Danilova, Ludmila ;

Davidsen, Tanja ;

Demchok, John A. ;

DiCara, Daniel ;

Dhalla, Noreen .

CELL, 2014, 159 (03) :676-690

[2] Generation of functional thyroid from embryonic stem cells [J].

Antonica, Francesco ;

Kasprzyk, Dominika Figini ;

Opitz, Robert ;

Iacovino, Michelina ;

Liao, Xiao-Hui ;

Dumitrescu, Alexandra Mihaela ;

Refetoff, Samuel ;

Peremans, Kathelijne ;

Manto, Mario ;

Kyba, Michael ;

Costagliola, Sabine .

NATURE, 2012, 491 (7422) :66-U170

[3] Directed differentiation of mouse embryonic stem cells into thyroid follicular cells [J].

Arufe, Maria C. ;

Lu, Min ;

Kubo, Atsushi ;

Keller, Gordon ;

Davies, Terry F. ;

Lin, Reigh-Yi .

ENDOCRINOLOGY, 2006, 147 (06) :3007-3015

[4] Differentiation of murine embryonic stern cells to thyrocytes requires insulin and indulin-like growth factor-1 [J].

Arufe, Maria C. ;

Lu, Min ;

Lin, Reigh-Yi .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 381 (02) :264-270

[5] When thyroid hormone replacement is ineffective? [J].

Benvenga, Salvatore .

CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY, 2013, 20 (05) :467-477

[6] An integrated analysis of cancer genes in thyroid cancer [J].

Chai, Li ;

Li, Jia ;

Lv, Zhongwei .

ONCOLOGY REPORTS, 2016, 35 (02) :962-970

[7] Significance of the BRAF mRNA Expression Level in Papillary Thyroid Carcinoma: An Analysis of The Cancer Genome Atlas Data [J].

Chai, Young Jun ;

Yi, Jin Wook ;

Jee, Hyeon-Gun ;

Kim, Young A. ;

Kim, Ju Han ;

Xing, Mingzhao ;

Lee, Kyu Eun .

PLOS ONE, 2016, 11 (07)

[8] Defining Adult Stem Cells by Function, not by Phenotype [J].

Clevers, Hans ;

Watt, Fiona M. .

ANNUAL REVIEW OF BIOCHEMISTRY, VOL 87, 2018, 87 :1015-1027

[9] High incidence of non-random template strand segregation and asymmetric fate determination in dividing stem cells and their progeny [J].

Conboy, Michael J. ;

Karasov, Ariela O. ;

Rando, Thomas A. .

PLOS BIOLOGY, 2007, 5 (05) :1120-1126

[10] New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma [J].

Costa, Valerio ;

Esposito, Roberta ;

Ziviello, Carmela ;

Sepe, Romina ;

Bim, Larissa Valdemarin ;

Cacciola, Nunzio Antonio ;

Decaussin-Petrucci, Myriam ;

Pallante, Pierlorenzo ;

Fusco, Alfredo ;

Ciccodicola, Alfredo .

ONCOTARGET, 2015, 6 (13) :11242-11251

← 1 2 3 4 5 6 →