Dedifferentiation of human primary thyrocytes into multilineage progenitor cells without gene introduction.
Dedifferentiation of human primary thyrocytes into multilineage progenitor cells without gene introduction.
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DOI：
10.1371/journal.pone.0019354
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发表时间：
2011-04-27
期刊：
影响因子：
3.7
通讯作者：
Yamashita S
中科院分区：
文献类型：
--
作者：
Suzuki K;Mitsutake N;Saenko V;Suzuki M;Matsuse M;Ohtsuru A;Kumagai A;Uga T;Yano H;Nagayama Y;Yamashita S
虽然成体干细胞的鉴定和分离具有潜在的重要意义，但最近关于分化细胞的去分化/重编程的报道为深入了解组织干细胞/祖细胞的来源提供了另一条线索。在这项研究中，我们开发了一种新的培养系统，从正常人甲状腺组织中获得去分化祖细胞。酶消化后，原代甲状腺细胞，表达甲状腺球蛋白，波形蛋白和细胞角蛋白-18，培养在无血清培养基称为SAGM。虽然绝大多数细胞死亡，但一小部分（约0.5%）存活并增殖。在最初的细胞扩增过程中，甲状腺球蛋白/细胞角蛋白-18的表达在增殖细胞中逐渐下降。此外，表达甲状腺过氧化物酶的分选细胞在SAGM中产生增殖克隆。这些数据表明，这些细胞来自甲状腺滤泡细胞或至少甲状腺定向细胞。SAGM培养的细胞不表达任何甲状腺特异性基因。然而，与FBS和TSH孵育4周后，细胞角蛋白-18，甲状腺球蛋白，TSH受体，PAX 8和TTF 1的表达重新出现。此外，令人惊讶的是，细胞能够根据分化条件分化成神经元或脂肪形成谱系。总之，我们已经开发了一种新的系统，从正常人甲状腺组织中产生多系祖细胞。这似乎是通过甲状腺滤泡细胞的去分化来实现的。目前描述的培养系统可能对再生医学有用，但首要的是作为阐明甲状腺疾病机制的工具。
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.
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影响因子：
3.4
作者：
BULEY, ID;GATTER, KC;MASON, DY
通讯作者：
MASON, DY
影响因子：
5.2
作者：
Ma, Wenxin;Yan, Run-Tao;Li, Xiumei;Wang, Shu-Zhen
通讯作者：
Wang, Shu-Zhen
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
23.9
作者：
Ichida JK;Blanchard J;Lam K;Son EY;Chung JE;Egli D;Loh KM;Carter AC;Di Giorgio FP;Koszka K;Huangfu D;Akutsu H;Liu DR;Rubin LL;Eggan K
通讯作者：
Eggan K
影响因子：
3.6
作者：
Richter, M;Tscheudschilsuren, G;Nieber, K
通讯作者：
Nieber, K