Identification of master transcription factors in corneal epithelial cells

角膜上皮细胞中主转录因子的鉴定

• 批准号: 23390404
• 负责人: KINOSHITA Shigeru
• 金额: $ 12.06万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390404/
• 关键词: 角膜上皮; 転写因子; ダイレクトリプログラミング; コア転写因子; マスターレギュレーター; 角膜上皮細胞; コア因子; 形質転換; エピゲノム

We attempted to identify master transcription factors (TFs) in corneal epithelial cells (CECs) which are able to maintain the cell-type specific transcriptional profile. First, we used microarray analysis to select candidate master TFs in CECs from all the genes, which were highly expressed in CECs compared to various other cells. In order to narrow down the master TFs in CECs, iPS interference screening was performed and produced 20 candidate TFs. A particular combination of candidate TFs was able to induce CEC-like cells expressing keratin 12, which is a corneal specific marker when overexpressed in a heterologous cell type. Furthermore, the expression level of other corneal-related genes, such as keratin 3, keratin 15, aldehyde dehydrogenase 3, transketolase, and E-cadherin were upregulated in the induced cells. These results suggested that defined TFs, which enabled the induction of CECs, contributed to the maintenance of the corneal-specific transcriptional profile.

我们试图鉴定角膜上皮细胞（CEC）中能够维持细胞类型特异性转录谱的主转录因子（TF）。首先，我们使用微阵列分析从所有基因中选择CEC中的候选主TF，与各种其他细胞相比，这些基因在CEC中高表达。为了缩小CEC中的主TF的范围，进行了iPS干扰筛选并产生了20个候选TF。候选TF的特定组合能够诱导表达角蛋白12的CEC样细胞，当角蛋白12在异源细胞类型中过度表达时，角蛋白12是角膜特异性标记物。此外，其他角膜相关基因，如角蛋白3、角蛋白15、乙醛脱氢酶3、转酮醇酶和E-钙粘蛋白的表达水平在诱导细胞中上调。这些结果表明，能够诱导 CEC 的特定 TF 有助于维持角膜特异性转录谱。

项目成果

Enhancement of corneal endothelium wound healing by a ROCK inhibitor eye drop

ROCK抑制剂滴眼液促进角膜内皮伤口愈合

• 发表时间: 2011
• 期刊: Br J Ophthalmol
• 作者: Okumura N;Koizumi N;Ueno M;Sakamoto Y;Takahashi H;Hirata K;Torii R;Hamuro J;Kinoshita S
• 通讯作者: Kinoshita S

Development of a Human Cultivated Nasal Mucosal Epithelial Cell Sheet for the Treatment of Severe Ocular Surface Diseases.

开发用于治疗严重眼表疾病的人类培养鼻粘膜上皮细胞片。

• 发表时间: 2013
• 作者: Masakazu Kobayashi;Takahiro Nakamura;Makoto Yasuda;Yuiko Hata;Shoki Okura;Naoki Okumura;Noriko Koizumi;Hisao Yasu;Shigeru Kinoshita
• 通讯作者: Shigeru Kinoshita

Investigation of gene therapy using immortalized cells derived from a Gelatioous Drop-Like Dystrophy patient

使用来自凝胶状水滴样营养不良症患者的永生化细胞进行基因治疗的研究

• 发表时间: 2013
• 期刊: Invest Ophthalmol Vis Sci
• 作者: Kitazawa K;Kawasaki S;Aoi K;Shinomiya K;Matsuda A;Funaki T;Nakatsukasa M;Murakami A;Kinoshita S
• 通讯作者: Kinoshita S

Two novel mutations of TACSTD2 found in three Japanese gelatinous drop-like corneal dystrophy families with their aberrant subcellular localization

在三个日本凝胶状水滴样角膜营养不良家族中发现 TACSTD2 的两种新突变及其异常的亚细胞定位

• 发表时间: 2011
• 期刊: Molecular Vision
• 影响因子: 2.2
• 作者: Nakatsukasa M;Kawasaki S;et.al.
• 通讯作者: et.al.

Proliferation propensity of cultured human corneal endothelial cells and their plasticity dictated by culture micro-environments

培养的人角膜内皮细胞的增殖倾向及其由培养微环境决定的可塑性

• 发表时间: 2013
• 作者: Munetoyo Toda;Morio Ueno;Kana Nakata;Kazuko Asada;Michio Hagiya;Naoki Okumura;Noriko Koizumi、Takahiro Nakamura;Junji Hamuro and Shigeru Kinoshita
• 通讯作者: Junji Hamuro and Shigeru Kinoshita