Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells.

Sumiyo Mimura, M. Suga, K. Okada, Masaki Kinehara, H. Nikawa, M. Furue
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引用次数: 25

Abstract

Neural crest (NC) cells are a group of cells located in the neural folds at the boundary between the neural and epidermal ectoderm. Cranial NC cells migrate to the branchial arches and give rise to the majority of the craniofacial region, whereas trunk and tail NC cells contribute to the heart, enteric ganglia of the gut, melanocytes, sympathetic ganglia, and adrenal chromaffin cells. Positional information is indispensable for the regulation of cranial or trunk and tail NC cells. However, the mechanisms underlying the regulation of positional information during human NC induction have yet to be fully elucidated. In the present study, supplementation of bone morphogenetic protein (BMP) 4 in defined serum-free culture conditions including fibroblast growth factor-2 and Wnt3a from day 8 after NC specification induced the expression of cranial NC markers, AP2alpha, MSX1, and DLX1, during NC cell differentiation from human pluripotent stem cells. On the other hand, the proportion of cells expressing p75(NTR) or HNK1 decreased compared with that of cells cultured without BMP4, whereas gene expression analysis demonstrated that the expression levels of cranial NC-associated genes increased in BMP4-treated NC cells. These BMP4-treated NC cells were capable of differentiation into osteocytes and chondrocytes. The results of the present study indicate that BMP4 regulates cranial positioning during NC development.
骨形态发生蛋白4促进人多能干细胞诱导颅面神经嵴。
神经嵴细胞(Neural crest cells, NC)是一组位于神经与表皮外胚层交界的神经褶皱中的细胞。颅NC细胞迁移到鳃弓并形成颅面区域的大部分,而躯干和尾部NC细胞则迁移到心脏、肠道的肠神经节、黑素细胞、交感神经节和肾上腺染色质细胞。位置信息对于颅内或干尾NC细胞的调控是必不可少的。然而,人体NC诱导过程中位置信息调控的机制尚未完全阐明。在本研究中,在NC规范后第8天,在确定的无血清培养条件下补充骨形态发生蛋白(BMP) 4,包括成纤维细胞生长因子-2和Wnt3a,诱导颅骨NC标记物AP2alpha, MSX1和DLX1的表达,在NC细胞从人多能干细胞分化过程中。另一方面,与未培养BMP4的NC细胞相比,表达p75(NTR)或HNK1的细胞比例下降,而基因表达分析表明,BMP4处理的NC细胞中颅NC相关基因的表达水平升高。这些bmp4处理的NC细胞能够分化为骨细胞和软骨细胞。本研究结果表明,BMP4在NC发育过程中调节颅骨定位。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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