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低氧条件促进人嗅黏膜间充质干细胞的增殖及相关 lncRNA 和 mRNA 分析。

Hypoxic conditioned promotes the proliferation of human olfactory mucosa mesenchymal stem cells and relevant lncRNA and mRNA analysis.

机构信息

Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China.

National Health Commission Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, Hunan, PR China; Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, PR China; Hunan Provincial Key Laboratory of Neurorestoratology, Second Affiliated Hospital of Hunan Normal University, Changsha 410003, Hunan, PR China.

出版信息

Life Sci. 2021 Jan 15;265:118861. doi: 10.1016/j.lfs.2020.118861. Epub 2020 Dec 7.


DOI:10.1016/j.lfs.2020.118861
PMID:33301811
Abstract

AIMS: LncRNAs are involved in many biological processes, and hypoxia contributed to the alterations of lncRNAs. Hypoxic preconditioned olfactory mucosa mesenchymal stem cells (OM-MSCs) exerted stronger anti-apoptotic ability in models of disease, but the molecules that controlled different biological characteristics of human OM-MSCs between hypoxic and normoxic conditions were unclear. The present study was aimed to explore the molecules that controlled different biological characteristics of human OM-MSCs between hypoxic and normoxic conditions. MAIN METHODS: LncRNAs and mRNAs expression profiles of human OM-MSCs between hypoxic (3%) and normoxic conditions were analyzed by Next-Generation Sequencing (NGS) analysis, bioinformatics analysis on these data were further performed. Moreover, loss-of function assay was conducted to investigate the impact of hypoxic condition on the proliferation and apoptosis of OM-MSCs. KEY FINDINGS: Through the comparative analysis and bioinformatics analysis, a total of 1741 lncRNAs and 1603 mRNAs were significant differentially expressed in the hypoxia group compared with normoxia group. Enrichment analysis revealed that differentially expressed genes of human OM-MSCs mainly participated in cell cycle regulation, secretin of cytokines and so on. Meanwhile, hypoxic condition significantly promoted proliferation and inhibited apoptosis of human OM-MSCs, following loss-of-function assays confirmed that lncRNA DARS-AS1 were involved in this regulatory process by hypoxic condition. Further prediction of targeted genes and the construction of lncRNA-miRNA-mRNA interaction network enriched the significance regarding the mechanism of DARS-AS1. SIGNIFICANCE: Altogether, these findings provided a new perspective for understanding the molecules expression patterns in hypoxia that contributed to corresponding phenotype alterations of OM-MSCs.

摘要

目的:长链非编码 RNA(lncRNAs)参与许多生物学过程,而缺氧会导致 lncRNAs 的改变。缺氧预处理的嗅黏膜间充质干细胞(OM-MSCs)在疾病模型中表现出更强的抗凋亡能力,但控制 OM-MSCs 在缺氧和常氧条件下不同生物学特性的分子尚不清楚。本研究旨在探讨控制 OM-MSCs 在缺氧和常氧条件下不同生物学特性的分子。

主要方法:通过下一代测序(NGS)分析分析 OM-MSCs 在缺氧(3%)和常氧条件下的 lncRNAs 和 mRNAs 表达谱,进一步对这些数据进行生物信息学分析。此外,还进行了功能丧失实验,以研究缺氧条件对 OM-MSCs 增殖和凋亡的影响。

主要发现:通过比较分析和生物信息学分析,在缺氧组与常氧组相比,共鉴定出 1741 个 lncRNAs 和 1603 个 mRNAs 显著差异表达。富集分析表明,OM-MSCs 差异表达基因主要参与细胞周期调控、细胞因子分泌等过程。同时,缺氧条件显著促进 OM-MSCs 的增殖并抑制其凋亡,通过功能丧失实验进一步证实,lncRNA DARS-AS1 参与了这一调节过程。对靶向基因的进一步预测和 lncRNA-miRNA-mRNA 相互作用网络的构建丰富了 DARS-AS1 机制的意义。

意义:综上所述,这些发现为理解缺氧条件下 OM-MSCs 相应表型改变所涉及的分子表达模式提供了新的视角。

相似文献

[1]
Hypoxic conditioned promotes the proliferation of human olfactory mucosa mesenchymal stem cells and relevant lncRNA and mRNA analysis.

Life Sci. 2021-1-15

[2]
Extracellular vesicles derived from hypoxia-preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR-612.

J Nanobiotechnology. 2021-11-21

[3]
lncRNA-mRNA expression profiles and functional networks of mesenchymal stromal cells involved in monocyte regulation.

Stem Cell Res Ther. 2019-7-16

[4]
Hypoxic Culture Promotes Dopaminergic-Neuronal Differentiation of Nasal Olfactory Mucosa Mesenchymal Stem Cells via Upregulation of Hypoxia-Inducible Factor-1α.

Cell Transplant. 2017-8

[5]
Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy.

Stem Cell Res Ther. 2021-7-22

[6]
Differential expression profiles of long noncoding RNAs and mRNAs in human bone marrow mesenchymal stem cells after exposure to a high dosage of dexamethasone.

Stem Cell Res Ther. 2021-1-6

[7]
Hypoxic preconditioning enhances cell hypoxia tolerance and correlated lncRNA and mRNA analysis.

Life Sci. 2018-7-9

[8]
Screening and identification of differential-expressed RNAs in thrombin-induced in vitro model of intracerebral hemorrhage.

Mol Cell Biochem. 2024-10

[9]
Enhancement of angiogenic effects by hypoxia-preconditioned human umbilical cord-derived mesenchymal stem cells in a mouse model of hindlimb ischemia.

Cell Biol Int. 2016-1

[10]
Comparative miRNA-Based Fingerprinting Reveals Biological Differences in Human Olfactory Mucosa- and Bone-Marrow-Derived Mesenchymal Stromal Cells.

Stem Cell Reports. 2016-4-21

引用本文的文献

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[2]
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[3]
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Aging Dis. 2023-10-1

[4]
A novel hypoxic lncRNA, HRL-SC, promotes the proliferation and migration of human dental pulp stem cells through the PI3K/AKT signaling pathway.

Stem Cell Res Ther. 2022-6-28

[5]
Hypoxia-preconditioned mesenchymal stem cells attenuate microglial pyroptosis after intracerebral hemorrhage.

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[6]
Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy.

Stem Cell Res Ther. 2021-7-22

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