High glucose suppresses embryonic stem cell differentiation into neural lineage cells.
High glucose suppresses embryonic stem cell differentiation into neural lineage cells.
复制标题
高葡萄糖可抑制胚胎干细胞分化为神经谱系细胞。
DOI：
10.1016/j.bbrc.2016.02.117
复制
发表时间：
2016-04-01
影响因子：
3.1
通讯作者：
Yang P
中科院分区：
文献类型：
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作者：
Yang P;Shen WB;Reece EA;Chen X;Yang P
异常神经发生在人类糖尿病妊娠和糖尿病胚胎病动物模型的胚胎发育过程中。我们以前在糖尿病胚胎病小鼠模型中的研究表明，母体糖尿病的高葡萄糖延迟了发育中的神经上皮的神经发生，导致神经管缺陷。然而，在高葡萄糖受损的神经发生的基础过程是未知的。胚胎干（ES）细胞的神经发生为了解高糖条件下异常神经谱系发育提供了一个有价值的模型。ES细胞通常在高葡萄糖（约25 mM葡萄糖）中产生和维持。在此，小鼠ES细胞系E14逐渐适应并维持在低葡萄糖（5 mM）中，并成为葡萄糖响应性E14（GR-E14）系。高糖诱导GR-E14细胞内质网应激标志物CHOP。在低葡萄糖条件下，GR-E14细胞保留其多能性和分化成神经谱系细胞的能力。高糖抑制GR-E14细胞向神经干细胞（Sox 1和nestin阳性细胞）的分化。高糖还抑制GR-E14细胞向神经元（Tuj 1阳性细胞）和胶质细胞（GFAP阳性细胞）分化。此外，高葡萄糖通过减少神经嵴标志物配对框3（Pax 3）和配对框7（Pax 7）延迟GR-E14分化为神经嵴细胞。因此，高葡萄糖损害ES细胞向神经谱系细胞的分化。低葡萄糖适应和高葡萄糖响应性GR-E14细胞系是用于评估高葡萄糖对中枢神经系统发育的不利影响的有用的体外模型。
Abnormal neurogenesis occurs during embryonic development in human diabetic pregnancies and in animal models of diabetic embryopathy. Our previous studies in a mouse model of diabetic embryopathy have implicated that high glucose of maternal diabetes delays neurogenesis in the developing neuroepithelium leading to neural tube defects. However, the underlying process in high glucose-impaired neurogenesis is uncharacterized. Neurogenesis from embryonic stem (ES) cells provides a valuable model for understanding the abnormal neural lineage development under high glucose conditions. ES cells are commonly generated and maintained in high glucose (approximately 25 mM glucose). Here, the mouse ES cell line, E14, was gradually adapted to and maintained in low glucose (5 mM), and became a glucose responsive E14 (GR-E14) line. High glucose induced the endoplasmic reticulum stress marker, CHOP, in GR-E14 cells. Under low glucose conditions, the GR-E14 cells retained their pluripotency and capability to differentiate into neural lineage cells. GR-E14 cell differentiation into neural stem cells (Sox1 and nestin positive cells) was inhibited by high glucose. Neuron (Tuj1 positive cells) and glia (GFAP positive cells) differentiation from GR-E14 cells was also suppressed by high glucose. In addition, high glucose delayed GR-E14 differentiation into neural crest cells by decreasing neural crest markers, paired box 3 (Pax3) and paired box 7 (Pax7). Thus, high glucose impairs ES cell differentiation into neural lineage cells. The low glucose adapted and high glucose responsive GR-E14 cell line is a useful in vitro model for assessing the adverse effect of high glucose on the development of the central nervous system.