Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (10): 72-78.doi: 10.6040/j.issn.1671-7554.0.2017.1194

Previous Articles    

Effects of Notch1 on neural stem cell differentiation induced by all-trans retinoic acid

XU Jiaming, MA Aihua, CHEN Na, HAN Bo   

  1. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2017-12-04 Published:2022-09-27

PDF (PC)

67

Abstract: Objective To investigate the role of Notch1 in neural stem cell differentiation induced by all-trans retinoic acid and to reveal its effects on neural tube development. Methods The expressions of Notch1 in nestin, neurofilament(NF), glial fibrillary acidic protein(GFAP)and galactocerebroside(GALC)were identified with immunofluorescence. The neural stem cells were cultured in normal differentiation medium and the all-trans retinoic acid(ATRA)medium. The expressions of nestin, NF, GFAP and GALC on day 1, 3, 5 and 7 were detected with Western blotting. The neural stem cells were divided into 4 groups and treated with normal differentiation medium(group A), normal differentiation medium + DMSO(group B), normal differentiation media + DMSO + 25 μmol/L γ-secretase inhibitor(group C), and normal differentiation media + DMSO + 50 μmol/L γ-secretase inhibitors(group D). The expressions of Notch1 in these groups were detected with Western blotting. Results Nestin, NF, GFAP and GALC were positively expressed, and Notch1 distributed in the cell membrane and cytoplasm. In the normal differentiation medium, Notch1 山 东 大 学 学 报 (医 学 版)56卷10期 -徐加明,等.Notch1在全反式维甲酸诱导的神经干细胞分化中的作用 \=-significantly increased on day 5 compared with day 1, NF decreased significantly on day 5 compared with day 3, GFAP and GALC significantly decreased on day 5 compared with day 1. In the ATRA medium, Notch1 significantly reduced on day 7 compared with day 1, whereas NF, GFAP, and GALC significantly increased on day 7. In after adoling the γSI, the intracellular domain(NICD)of Notch1 decreased significantly. Conclusion Notch1 signal pathway inhibits neural stem cell differentiation, while ATRA promotes neural stem cell differentiation by inhibiting Notch1.

Key words: Neural tube defect, All-trans retinoic acid, Notch1, Neural stem cell

CLC Number: 

  • R729
[1] Ramdurg SR, Shubhi D, Vishal K. Multiple neural tube defects: a rare combination of limited dorsal myeloschisis, diplomyelia with dorsal bony spur, sacral meningocoele, syringohydromyelia, and tethered cord[J]. Childs Nerv Syst, 2017, 33(4): 699-701.
[2] Leung KY, De Castro SC, Savery D, et al. Nucleotide precursors prevent folic acid-resistant neural tube defects in the mouse[J]. Brain, 2013, 136(Pt 9): 2836-2841.
[3] Wilde J, Petersen J, Niswander L. Genetic, epigenetic, and environmental contributions to neural tube closure[J]. Annu Rev Genet, 2014, 48(1): 583-611.
[4] Mcshane SG, Molè MA, Savery D, et al. Cellular basis of neuroepithelial bending during mouse spinal neural tube closure[J]. Dev Biol, 2015, 404(2): 113-124
[5] Greene ND, Copp AJ. Neural tube defects[J]. Wiley Interdiscip Rev Dev Biol, 2013 Mar-Apr(2): 213-227.
[6] Mendonça LS, Nóbrega C, Hirai H, et al. Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in Machado-Joseph disease mice[J]. Brain, 2015, 138(Pt 2): 320-335.
[7] 幸华杰, 李梦桃, 宋青, 等. 神经干细胞分化调控机制的研究进展[J]. 解剖学报, 2014, 45(1): 140-144. XING Huajie, LI Mengtao, SONG Qing, et al. Progress in the studies of neural stem cell differentiation[J]. Acta Anatomica Sinica, 2014, 45(1): 140-144.
[8] Shi L, Ma Y, Zheng C, et al. The effect of blocking Notch signaling by Î3-secretase inhibitor on allergic rhinitis[J]. Int J Pediatr Otorhinolaryngol, 2017, 98: 32-38. doi: 10.1016/j.ijporl.2017.04.036.
[9] Redmond L, Oh SR, Hicks C, et al. Nuclear Notch1 signaling and the regulation of dendritic development[J]. Nat Neurosci, 2000, 3(1): 30-40.
[10] 李新军, 杨忠, 曾义, 等. 维甲酸诱导神经管发育缺陷相关基因表达验证[J]. 中华神经外科杂志, 2012, 28(12): 1279-1283. LI Xinjun, YANG Zhong, ZENG Yi, et al. Investigation of the differential gene expressions in neural tube defects through retinoic acid induction[J]. Chinese Journal of Neurosurgery, 2012, 28(12): 1279-1283.
[11] Sulik KK. Perspectives on R.E. Shenefelts 1972 Teratology publication entitled “Morphogenesis of malformations in hamsters caused by retinoic acid: relation to dose and stage at treatment”[J]. Birth Defects Res B Dev Reprod Toxicol, 2010, 89(4): 275-278.
[12] Zhai S, Zhao M, Zhou C, et al. The association and significance of H3K27me3 and a folate metabolic gene ACat2 in neural tube defects[J]. Nutr J, 2016, 15(1): 95.
[13] 徐鹏. 大鼠神经干细胞的体外培养及其条件培养基对骨髓间充质干细胞向神经干细胞分化的影响[D]. 合肥:安徽医科大学, 2014.
[14] Badouel C, Zander MA, Liscio N, et al. Fat1 interacts with Fat4 to regulate neural tube closure, neural progenitor proliferation and apical constriction during mouse brain development[J]. Development, 2015, 142(16): 2781-2791.
[15] Zhu X, Li B, Ai Z, et al. A robust single primate neuroepithelial cell clonal expansion system for neural tube development and disease studies[J]. Stem Cell Reports, 2016, 6(2): 228-242.
[16] Yamashita M. From neuroepithelial cells to neurons: changes in the physiological properties of neuroepithelial stem cells[J]. Arch Biochem Biophys, 2013, 534(1-2): 64-70.
[17] 郭红梅, 王晓梅. Notch信号通路在神经干细胞分化与再生的研究进展[J]. 中国临床神经科学, 2013, 21(4): 463-467. GUO Hongmei,WANG Xiaomei. Research progress of the notch signaling pathway in neural stem cell differentiation and regeneration[J]. Chinese Journal of Clinical Neurosciences, 2013, 21(4): 463-467.
[18] Mao YZ, Jiang L.Effects of Notch signalling pathway on the relationship between vascular endothelial dysfunction and endothelial stromal transformation in atherosclerosis.[J]. Artif Cells Nanomed Biotechnol, 2018, 46(4): 764-772.
[19] Du M, Tan Y, Liu G, et al. Effects of the Notch signalling pathway on hyperoxia-induced immature brain damage in newborn mice[J]. Neurosci Lett, 2017,653: 220-227. doi: 10.1016/j.neulet.2017.05.065.
[20] Venkatesh K, Lvk R, Abbas S, et al. NOTCH signaling is essential for maturation, self-renewal, and tri-differentiation of in vitro derived human neural stem cells[J]. Cell Reprogram, 2017, 19(6): 372-383.
[21] Zhang J, Li R, He Q, et al. All-trans-retinoic acid alters Smads expression in embryonic neural tissue of mice[J]. J Appl Toxicol, 2009, 29(4): 364-366.
[22] Abdyazdani N, Nourazarian A, Charoudeh HN, et al. The role of morphine on rat neural stem cells viability, neuro-angiogenesis and neuro-steroidgenesis properties[J]. Neurosci Lett, 2017, 636:205-212. doi: 10.1016/j.neulet.2016.11.025.
[23] Kiparissides A, Koutinas M, Moss T, et al. Modelling the Delta1/notch1 pathway: in search of the mediator(s)of neural stem cell differentiation[J]. PLoS One, 2011, 6(2): e14668. doi: 10.1371/journal.pone.0014668
[24] Cheng YL, Choi Y, Sobey CG, et al. Emerging roles of the γ-secretase-notch axis in inflammation[J]. Pharmacol Ther, 2015, 147: 80-90. doi: 10.1016/j.pharmthera.2014.11.005.
[25] Yan Y, Kong L, Xia Y, et al. Osthole promotes endogenous neural stem cell proliferation and improved neurological function through Notch signaling pathway in mice acute mechanical brain injury[J]. Brain Behav Immun, 2018, 67: 118-129. doi: 10.1016/j.bbi.2017.08.011.
[1] LIANG Yu, XIN Tao, LIU Qian, ZHENG Xiangrong, YANG Yihang, PANG Qi. Effects of theanine on the proliferation and differentiation of neural stem cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 49-54.
[2] ZHU Yuhua1, YUAN Honghua2, WU Lianlian2, HU Ankang1, CHEN Renjin1, ZHU Xiaorong1. Insulin-like growth factor-1 induces neural stem cells to differentiate into neurons via PI3K/Akt signaling pathway [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(3): 11-15.
[3] FANG Min1, BI Ke-hong2, JIANG Guo-sheng3, ZHU Chuan-sheng2. Changes of the LMP/TAP gene expressions and its significance in leukemia cells HL-60 after induced differentiation [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(2): 1-5.
[4] BAO Dan-dan, LI Ping, CHU Hong-shang, LIU Hui-juan. Effects of bone morphogenetic protein-2 on the proliferation and differentiation of neural stem cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(1): 10-14.
[5] HE Jun-feng1, LIU Jun2, WANG Wei-ren3, ZHANG Qing-feng1, YANG Qiong-fen1, LI Guang-you1， ZHOU Lin1， LI Zhi-mei1, LI Pei-zhen1 . A case-control study on the risk factors of neural tube defects in Guizhou province of China [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(7): 50-53.
[6] ZHANG Bing-zhen, DAI Bing-qin, ZHANG Xing-liang, WANG Zhi-ping. Associations of maternal methionine synthase A2756G and methionine synthase reductase A66G polymorphisms with neural tube defects of the offspring: A meta-analysis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(7): 125-132.
[7] LI Heng1, LI Xiao-hong2, BI Jian-fen3, CHEN Ya-na4. All-trans retinoic acid promoted human umbilical cord blood derived
multipotent stem cells to differentiate into dopaminergic neurons [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(6): 92-96.
[8] ZHANG Jing1, GAO Ying-mao2, SUN Jin-hao1, BAO Li-hua1. Cloning and relativity analysis of gene CDK109 related to neural tube defects induced by hyperthermia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(1): 19-.
[9] GONG Rui1, MENG Cai2, SUN Xihong1, WANG Zhiping1, ZHAO Zhongtang1. Effect of pregnancy planning on primary prevention measures for neural tube defects [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(4): 142-146.
[10] . Effect of silencing Notch1 on proliferation of bladder cancer cell line T24 [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(9): 53-57.
[11] . Relationship between gene expression of βcatenin and  embryonic neural tube defects induced by Retinoic acid [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(8): 45-49.
[12] HAO Lianzheng, LI Hui, WANG Zhiping, ZHAO Zhongtang
. Effects of integrated intervention measurements on neural tube
defects in Chinese women of childbearing age
 [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(04): 117-121.
[13] MA Yong-zhen,WU Yu-ling. Expression and significance of Connexin 43 on neural epithelium during neural tube defects [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(12): 1209-1212.
[14] WANG Xin-yu,LI Xin-gang,ZHOU Lu,BAO Xiu-feng,XIN Hua. Effect of striatal extracts on inducing the NSC differentiate into dopaminergic neurons: an experimental study [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(11): 1168-1171.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd