S100A9 promotes apical-basal polarity and neural tube formation during differentiation of embryonic stem cells into neural progenitor cells

您当前的位置：

首页 >

文章列表页 >

S100A9 promotes apical-basal polarity and neural tube formation during differentiation of embryonic stem cells into neural progenitor cells

Neurosciences | 更新时间：2026-01-09

- S100A9 promotes apical-basal polarity and neural tube formation during differentiation of embryonic stem cells into neural progenitor cells
- Journal of Army Medical University Vol. 45, Issue 1, Pages: 10-18(2023)
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院神经外科
- 作者简介：
- 基金信息：
  
  the General Program of Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0036)
- DOI：10.16016/j.2097-0927.202204002
  CLC： R322.8;R318;R329.24
- Received：01 April 2022，
  
  Revised：2022-06-08，
  
  Published：15 January 2023
- 稿件说明：
移动端阅览
Xiang ZHANG, Jianhe YUE, Ning HUANG. S100A9 promotes apical-basal polarity and neural tube formation during differentiation of embryonic stem cells into neural progenitor cells[J]. Journal of Army Medical University, 2023, 45(1): 10-18.
DOI：

Xiang ZHANG, Jianhe YUE, Ning HUANG. S100A9 promotes apical-basal polarity and neural tube formation during differentiation of embryonic stem cells into neural progenitor cells[J]. Journal of Army Medical University, 2023, 45(1): 10-18. DOI： 10.16016/j.2097-0927.202204002.

摘要

目的

2

探讨胚胎干细胞(embryonic stem cells

ESCs)向神经前体细胞(neural progenitor cells

NPCs)分化过程中S100A9促进顶端-基底极化(apical-basal polarity

ABP)和神经管结构形成的作用。

方法

2

采用免疫荧光观察体外培养ESCs向NPCs分化1、2、3和6 d时细胞管腔样结构排列，神经巢蛋白(Nestin)和配对盒因子6(paired box protein 6

Pax-6)表达，以及S100A9、N-钙粘蛋白(N-cadherin)和zonula occludens 1(ZO-1)定位变化。慢病毒转染下调S100A9及外源性S100A9重组蛋白干预细胞后检测对N-cadherin和ZO-1定位的影响。Western blot分析S100A9在ESCs向NPCs分化过程中不同时间点表达差异，同时观察S100A9对Notch1及下游centromere binding factor 1(CBF1)的调控。

结果

2

ESCs在体外定向分化后第3天起表达Nestin和Pax-6，N-cadherin和ZO-1定位于顶端侧并呈现出ABP特征性神经玫瑰花状结构(neural rosette)，细胞在第6天形成神经管结构。S100A9在分化后第3天起表达明显增加(

P

<

0.01)并定位于顶端侧。下调S100A9后ESCs仍能分化为NPCs，但neural rosette数量明显减少(

P

<

0.01)。予以外源性S100A9重组蛋白可部分恢复neural rosette数量(

P

<

0.01)。在此分化过程中，下调S100A9降低Notch1及下游CBF1表达。

结论

2

S100A9可能通过调控Notch1/CBF1参与ESCs向NPCs分化过程中ABP和神经管结构形成。

Abstract

Objective

2

To explore the role of S100A9 in the apical-basal polarity (ABP) and neural tube formation during the differentiation of embryonic stem cells (ESCs) into neural progenitor cells (NPCs)

in vitro

.

Methods

2

Immunofluorescence assay was used to observe the luminal arrangement

expression of Nestin and paired box protein 6 (Pax-6)

and localization of S100A9

N-cadherin and Zonula occludens 1 (ZO-1) on days 1

2

3 and 6 of the ESCs differentiation into NPCs. In addition

the ESCs were treated with S100A9-downregulation lentivirus as well as subsequential exogenous S100A9 recombinant protein

then the localization changes of N-cadherin and ZO-1 were detected. The S100A9 expression in different time points during ESCs differentiation process was measured by Western blotting

and the effects of S100A9 on Notch1 and downstream centromere binding factor 1 (CBF1) were also tested.

Results

2

Nestin and Pax-6 were positively expressed after ESCs differentiation for 3 d

N-cadherin and ZO-1 were gathered at the apical side and presented the characteristic neural rosette structure of ABP

and the neural tubes were formed on day 6. The expression of S100A9 was upregulated significantly from day 3 after differentiation (

P

<

0.01) and was located on the apical side. Although ESCs were still able to differentiate into NPCs after down-regulation of S100A9

the number of neural rosettes was greatly reduced (

P

<

0.01)

which could be partially restored by supplement of exogenous S100A9 recombinant protein (

P

<

0.01). Furthermore

declined S100A9 inhibited the expression of Notch 1 and downstream CBF1 during differentiation.

Conclusion

2

S100A9 may contribute to the ABP and the formation of neural lumen during the differentiation of ESCs into NPCs by regulating Notch 1/CBF1.

关键词

Keywords

references

MOJALLAL M, ZHENG Y J, HULTIN S, et al . AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion[J ] . Nat Commun, 2014, 5: 4557. DOI:10.1038/ncomms5557.

MEDELNIK J P, ROENSCH K, OKAWA S, et al . Signaling -dependent control of apical membrane size and self-renewal in rosette-stage human neuroepithelial stem cells[J ] . Stem Cell Reports, 2018, 10(6): 1751-1765. DOI:10.1016/j.stemcr.2018.04.018.

MAIN H, RADENKOVIC J, JIN S B, et al . Notch signaling maintains neural rosette polarity[J ] . PLoS One, 2013, 8(5): e62959. DOI:10.1371/journal.pone.0062959.

WANG S W, SONG R, WANG Z Y, et al . S100A8/A9 in inflammation[J ] . Front Immunol, 2018, 9: 1298. DOI:10.3389/fimmu.2018.01298.

TIAN Y, CAO R, CHE B C, et al . Proinflammatory S100A9 regulates differentiation and aggregation of neural stem cells[J ] . ACS Chem Neurosci, 2020, 11(21): 3549-3556. DOI:10.1021/acschemneuro.0c00365.

HOLDHOF D, SCHOOF M, AL-KERSHI S, et al . Brahma-related gene 1 has time-specific roles during brain and eye development[J ] . Development, 2021, 148(10): dev196147. DOI:10.1242/dev.196147.

JEON K, PARK K, JETTEN A M. Efficient neural differentiation using single-cell culture of human embryonic stem cells[J]. J Vis Exp, 2020(155): 10.3791/60571. DOI:10.3791/60571.

GRABIEC M, HRŘÍBKOVÁ H, VARŘECHA M, et al . Stage-specific roles of FGF2 signaling in human neural development[J ] . Stem Cell Res, 2016, 17(2): 330-341. DOI:10.1016/j.scr.2016.08.012.

BROCCOLI V, GIANNELLI S G, MAZZARA P G. Modeling physiological and pathological human neurogenesis in the dish[J]. Front Neurosci, 2014, 8: 183. DOI:10.3389/fnins.2014.00183.

TOWNSHEND R F, SHAO Y, WANG S C, et al . Effect of cell spreading on rosette formation by human pluripotent stem cell-derived neural progenitor cells[J ] . Front Cell Dev Biol, 2020, 8: 588941. DOI:10.3389/fcell.2020.588941.

COULTHARD L G, HAWKSWORTH O A, LI R, et al . Complement C5aR1 signaling promotes polarization and proliferation of embryonic neural progenitor cells through PKCζ[J ] . J Neurosci, 2017, 37(22): 5395-5407. DOI:10.1523/JNEUROSCI.0525-17.2017.

JUKIC A, BAKIRI L, WAGNER E F, et al . Calprotectin: from biomarker to biological function[J ] . Gut, 2021, 70(10): 1978-1988. DOI:10.1136/gutjnl-2021-324855.

MA L, SUN P, ZHANG J C, et al . Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells[J ] . Int J Mol Med, 2017, 40(1): 31-38. DOI:10.3892/ijmm.2017.2987..

LIU S, XIE Y, LUO W, et al . PE_PGRS31-S100A9 interaction promotes mycobacterial survival in macrophages through the regulation of NF-κB-TNF-α signaling and arachidonic acid metabolism[J ] . Front Microbiol, 2020, 11: 845. DOI:10.3389/fmicb.2020.00845.

CREMERS N A J, VAN DEN BOSCH M H J, VAN DALEN S, et al . S100A8/A9 increases the mobilization of pro-inflammatory Ly6C high monocytes to the synovium during experimental osteoarthritis[J ] . Arthritis Res Ther, 2017, 19(1): 217. DOI:10.1186/s13075-017-1426-6.

CHEN J C, DONG X X, CHENG X J, et al . Ogt controls neural stem/progenitor cell pool and adult neurogenesis through modulating Notch signaling[J ] . Cell Rep, 2021, 34(13): 108905. DOI:10.1016/j.celrep.2021.108905.

ZHANG R R, ENGLER A, TAYLOR V. Notch: an interactive player in neurogenesis and disease[J]. Cell Tissue Res, 2018, 371(1): 73-89. DOI:10.1007/s00441-017-2641-9.

NOISA P, LUND C, KANDURI K, et al . Notch signaling regulates the differentiation of neural crest from human pluripotent stem cells[J ] . J Cell Sci, 2014, 127(Pt 9): 2083-2094. DOI:10.1242/jcs.145755.

HUANG N, ZHAO G J, YANG Q, et al . Intracellular and extracellular S100A9 trigger epithelial-mesenchymal transition and promote the invasive phenotype of pituitary adenoma through activation of AKT1[J ] . Aging (Albany NY), 2020, 12(22): 23114-23128. DOI:10.18632/aging.104072.

HUANG N, CHEN S, DENG J M, et al . Overexpression of S100A9 in human glioma and in-vitro inhibition by aspirin[J ] . Eur J Cancer Prev, 2013, 22(6): 585-595. DOI:10.1097/CEJ.0b013e328364f1c9..

0

Views

0

下载量

0

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Related Articles

Screening and identification of genes for exiting naïve pluripotency in embryonic stem cells using the CRISPR-Cas9 knockout system

Effect of RNA interference-mediated S100A9 gene silencing on proliferation and self-renewal of U87 glioma stem cells in vitro

Development of microfluid cell electro-fusion chip and its application in somatic cell reprogramming

Construction of S100A9 eukaryotic expression vector and its effect on proliferation of glioma cell line U251

Pulsed electromagnetic fields induce osteoblast differentiation from mouse embryonic stem cells in vitro

Related Author

RUAN Yan

ZHANG Junlei

TIAN Yanping

YU Meng

LI Hongli

YANG Yi

Gang HUO

Song CHEN

Related Institution

Experimental Center of Basic Medicine, Pu’er

Department of Histology and Embryology， College of Basic Medical Sciences， Army Medical University （Third Military Medical University）， Chongqing, Pu’er

Department of Neuroendocrine， Rheumatic and Immunologic Diseases， No. Hospital of Joint Logistics Support Force927， Pu’er

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University

⁰