Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells.
Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells.
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DOI：
10.1371/journal.pone.0028856
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shimmura S
中科院分区：
文献类型：
--
作者：
Yoshida S;Yasuda M;Miyashita H;Ogawa Y;Yoshida T;Matsuzaki Y;Tsubota K;Okano H;Shimmura S
诱导多能干细胞（iPS）在再生医学中的应用将绕过与使用胚胎干细胞相关的伦理问题。此外，患者特异性IPS细胞可用于阐明遗传性疾病的病理生理学、药物筛选和定制药物。然而，为了将iPS细胞应用于有丝分裂组织，需要诱导产生靶器官后代的组织干细胞。我们使用BMP 4通过与PA 6饲养细胞共培养（SDIA方法）从小鼠iPS细胞诱导分层上皮细胞。在KRT 14阳性集落中观察到分化标志物KRT 1或KRT 12阳性的细胞簇。我们成功地克隆了KRT 14和p63双阳性分层上皮祖细胞从iPS衍生的上皮细胞，形成分层上皮片组成的五至六极化上皮细胞在体外。当这些克隆细胞培养在裸露的小鼠角膜上时，观察到具有生理细胞极性的稳健的复层上皮层，包括基底层中的高水平的E-钙粘蛋白、p63和K15表达以及浅表层中的ZO-1表达，重现了体内上皮的顶端-基底极性。这些结果表明，KRT 14和p63双阳性上皮祖细胞可以从iPS细胞克隆，以产生极化的多层上皮细胞片。
Application of induced pluripotent stem (iPS) cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, and tailor-made medicine. However, in order to apply iPS cells to mitotic tissue, induction of tissue stem cells that give rise to progeny of the target organ is required. We induced stratified epithelial cells from mouse iPS cells by co-culture with PA6 feeder cells (SDIA-method) with use of BMP4. Clusters of cells positive for the differentiation markers KRT1 or KRT12 were observed in KRT14-positive colonies. We successfully cloned KRT14 and p63 double-positive stratified epithelial progenitor cells from iPS-derived epithelial cells, which formed stratified epithelial sheets consisting of five- to six-polarized epithelial cells in vitro. When these clonal cells were cultured on denuded mouse corneas, a robust stratified epithelial layer was observed with physiological cell polarity including high levels of E-cadherin, p63 and K15 expression in the basal layer and ZO-1 in the superficial layer, recapitulating the apico-basal polarity of the epithelium in vivo. These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can be cloned from iPS cells in order to produce polarized multilayer epithelial cell sheets.
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影响因子：
--
作者：
Ji, Lin;Allen-Hoffmann, B. Lynn;Palecek, Sean P.
通讯作者：
Palecek, Sean P.
影响因子：
5.2
作者：
Metallo, Christian M.;Ji, Lin;Palecek, Sean P.
通讯作者：
Palecek, Sean P.
影响因子：
0.7
作者：
Pearton, DJ;Ferraris, C;Dhouailly, D
通讯作者：
Dhouailly, D
影响因子：
4.1
作者：
Nakamura, T;Inatomi, T;Kinoshita, S
通讯作者：
Kinoshita, S
DOI：
10.1073/pnas.1037282100
发表时间：
2003-05-13
影响因子：
11.1
作者：
Mizuseki, K;Sakamoto, T;Sasai, Y
通讯作者：
Sasai, Y