title: Dedifferentiation of human primary thyrocytes into multilineage progenitor cells without gene introduction.
abstract: While identification and isolation of adult stem cells have potentially important implications, recent reports regarding dedifferentiation/reprogramming from differentiated cells have provided another clue to gain insight into source of tissue stem/progenitor cells. In this study, we developed a novel culture system to obtain dedifferentiated progenitor cells from normal human thyroid tissues. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin, vimentin and cytokeratin-18, were cultured in a serum-free medium called SAGM. Although the vast majority of cells died, a small proportion (∼0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined in the proliferating cells. Moreover, sorted cells expressing thyroid peroxidase gave rise to proliferating clones in SAGM. These data suggest that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. In summary, we have developed a novel system to generate multilineage progenitor cells from normal human thyroid tissues. This seems to be achieved by dedifferentiation of thyroid follicular cells. The presently described culture system may be useful for regenerative medicine, but the primary importance will be as a tool to elucidate the mechanisms of thyroid diseases.
authors.affiliation: Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Vladimir
authors.initials: V
authors.lastname: Saenko
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Michiko
authors.initials: M
authors.lastname: Matsuse
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtsuru
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumagai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Uga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism
chemical_list: D017931:DNA Primers