Commitment of human pluripotent stem cells to a neural lineage is induced by the pro-estrogenic flavonoid apigenin

C. S. Souza, B. Paulsen, S. Devalle, Silvia Lima Costa, H. Borges, S. Rehen
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引用次数: 15

Abstract

Flavonoids are polyphenolic compounds that are ubiquitous in plants and have biological effects on cancer cells and other cell types. In particular, apigenin (API) has been shown to bind to estrogen receptors, which affect the development, maturation, function, and plasticity of the nervous system. The aim of this study was to investigate the effects of 4′,5,7-trihydroxyflavone (API) upon the neural differentiation of human pluripotent stem cells. Treatment of both human embryonic stem cells and human induced pluripotent stem cells with API increased the number of nestin (NES+) neural progenitor cells compared to untreated controls. API also induced the expression of neuronal markers, such as β-tubulin-III (TUBB3), microtubule-associated protein 2 (MAP2), polysialylated-neural cell adhesion molecule (PSA-NCAM), synapsin 1 (SYN1), neurofilament (NEF), choline acetyltransferase (CHAT), glutamate decarboxylase (GAD1), and parvalbumin (PVALB) proteins. Antagonists of estrogen receptors (ESR1 and ESR2) suppressed the effects of API. API-induced differentiation was followed by increased expression of retinoic acid (RA) receptors (RARA and RARB) and retinoic X receptor (RXR) G, but not RARG1 or RXRB. Neural differentiation induced by API was drastically reduced by the inhibition of RARs. In addition, API also increased synaptogenesis in RA-differentiated neurons. These findings suggest that API induces neural differentiation of human pluripotent stem cells through estrogen receptor and RAR signaling and improves their functional differentiation into neurons.
人类多能干细胞向神经谱系的承诺是由促雌激素类黄酮类芹菜素诱导的
黄酮类化合物是一种多酚类化合物,在植物中普遍存在,对癌细胞和其他类型的细胞有生物作用。特别是芹菜素(API)已被证明与雌激素受体结合,影响神经系统的发育、成熟、功能和可塑性。本研究旨在探讨4′,5,7-三羟基黄酮(API)对人多能干细胞神经分化的影响。与未处理的对照相比,用API处理的人胚胎干细胞和人诱导多能干细胞增加了巢蛋白(NES+)神经祖细胞的数量。API还诱导了神经元标志物的表达,如β-微管蛋白- iii (TUBB3)、微管相关蛋白2 (MAP2)、多唾液酸-神经细胞粘附分子(PSA-NCAM)、突触素1 (SYN1)、神经丝(NEF)、胆碱乙酰转移酶(CHAT)、谷氨酸脱羧酶(GAD1)和小白蛋白(PVALB)蛋白。雌激素受体(ESR1和ESR2)拮抗剂抑制API的作用。api诱导分化后,维甲酸(RA)受体(RARA和RARB)和维甲酸X受体(RXR) G的表达增加,但RARG1和RXRB的表达不增加。API诱导的神经分化由于RARs的抑制而明显减弱。此外,API还增加了ra分化神经元的突触发生。提示API通过雌激素受体和RAR信号通路诱导人多能干细胞神经分化,促进多能干细胞向神经元的功能分化。
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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