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源自小鼠诱导多能干细胞的颅神经嵴样细胞的阶段依赖性差异基因表达谱

Stage-dependent differential gene expression profiles of cranial neural crest-like cells derived from mouse-induced pluripotent stem cells.

作者信息

Odashima Ayano, Onodera Shoko, Saito Akiko, Ogihara Yuuki, Ichinohe Tatsuya, Azuma Toshifumi

机构信息

Department of Oral Health Science Center, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo, 101-0051, Japan.

Department of Biochemistry, Tokyo Dental College, Tokyo, Japan.

出版信息

Med Mol Morphol. 2020 Mar;53(1):28-41. doi: 10.1007/s00795-019-00229-2. Epub 2019 Jul 11.

Abstract

Cranial neural crest cells are multipotent cells that migrate into the pharyngeal arches of the vertebrate embryo and differentiate into various craniofacial organ derivatives. Therefore, migrating cranial neural crest cells are considered one of the most attractive candidate cell sources in regenerative medicine. We generated cranial neural crest like cell (cNCCs) using mouse-induced pluripotent stem cells cultured in neural crest-inducing medium for 14 days. Subsequently, we conducted RNA sequencing experiments to analyze gene expression profiles of cNCCs at different time points after induction. cNCCs expressed several neural crest specifier genes; however, some previously reported specifier genes such as paired box 3 and Forkhead box D3, which are essential for embryonic neural crest development, were not expressed. Moreover, ETS proto-oncogene 1, transcription factor and sex-determining region Y-box 10 were only expressed after 14 days of induction. Finally, cNCCs expressed multiple protocadherins and a disintegrin and metalloproteinase with thrombospondin motifs enzymes, which may be crucial for their migration.

摘要

颅神经嵴细胞是多能细胞,它们迁移到脊椎动物胚胎的咽弓中,并分化为各种颅面器官衍生物。因此,迁移的颅神经嵴细胞被认为是再生医学中最具吸引力的候选细胞来源之一。我们使用在神经嵴诱导培养基中培养14天的小鼠诱导多能干细胞生成了颅神经嵴样细胞(cNCCs)。随后,我们进行了RNA测序实验,以分析诱导后不同时间点cNCCs的基因表达谱。cNCCs表达了几种神经嵴特异性基因;然而,一些先前报道的对胚胎神经嵴发育至关重要的特异性基因,如配对盒3和叉头盒D3,并未表达。此外,ETS原癌基因1、转录因子和性别决定区Y盒10仅在诱导14天后表达。最后,cNCCs表达了多种原钙黏蛋白和具有血小板反应蛋白基序的解整合素和金属蛋白酶,这可能对它们的迁移至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a7/7033077/7a25f0873471/795_2019_229_Fig1_HTML.jpg

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