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Thyroid. 2017 Mar;27(3):460-474. doi: 10.1089/thy.2016.0130. Epub 2017 Feb 17.

An Adult Mouse Thyroid Side Population Cell Line that Exhibits Enriched Epithelial-Mesenchymal Transition.

Author information

1
1 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
2
2 DNA Sequencing and Genomics Core, National Heart, Lung, and Blood Institute , Bethesda, Maryland.
3
3 Electron Microscope Laboratory, Leidos Biomedical Research Inc. , Frederick National Laboratory for Cancer Research, Frederick, Maryland.
4
4 Systems Biology Center, National Heart, Lung, and Blood Institute , Bethesda, Maryland.

Abstract

BACKGROUND:

Studies of thyroid stem/progenitor cells have been hampered due to the small organ size and lack of tissue, which limits the yield of these cells. A continuous source that allows the study and characterization of thyroid stem/progenitor cells is desired to push the field forward.

METHOD:

A cell line was established from Hoechst-resistant side population cells derived from mouse thyroid that were previously shown to contain stem/progenitor-like cells. Characterization of these cells were carried out by using in vitro two- and three-dimensional cultures and in vivo reconstitution of mice after orthotopic or intravenous injection, in conjunction with quantitative reverse transcription polymerase chain reaction, Western blotting, immunohisto(cyto)chemistry/immunofluorescence, and RNA seq analysis.

RESULTS:

These cells were named SPTL (side population cell-derived thyroid cell line). Under low serum culturing conditions, SPTL cells expressed the thyroid differentiation marker NKX2-1, a transcription factor critical for thyroid differentiation and function, while no expression of other thyroid differentiation marker genes were observed. SPTL cells formed follicle-like structures in Matrigel® cultures, which did not express thyroid differentiation marker genes. In mouse models of orthotopic and intravenous injection, the latter following partial thyroidectomy, a few SPTL cells were found in part of the follicles, most of which expressed NKX2-1. SPTL cells highly express genes involved in epithelial-mesenchymal transition, as demonstrated by RNA seq analysis, and exhibit a gene-expression pattern similar to anaplastic thyroid carcinoma.

CONCLUSION:

These results demonstrate that SPTL cells have the capacity to differentiate into thyroid to a limited degree. SPTL cells may provide an excellent tool to study stem cells, including cancer stem cells of the thyroid.

KEYWORDS:

RNA seq analysis; epithelial-to-mesenchymal transition; thyroid cancer; thyroid side population; thyroid stem cells

PMID:
28125936
PMCID:
PMC5346910
DOI:
10.1089/thy.2016.0130
[Indexed for MEDLINE]
Free PMC Article

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