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NEL-like 1 蛋白诱导成骨分化过程中的长非编码 RNA 表达谱。

Long noncoding RNA expression profiles during the NEL-like 1 protein-induced osteogenic differentiation.

机构信息

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

J Cell Physiol. 2020 Sep;235(9):6010-6022. doi: 10.1002/jcp.29526. Epub 2020 Jan 27.

Abstract

Long noncoding RNAs (lncRNAs) are important modulators of mesenchymal stem cells (MSCs) in cellular differentiation. However, the regulatory mechanisms of lncRNAs in NEL-like 1 (NELL-1)-induced osteogenic differentiation of human adipose-derived stem cells remain elusive. Expression profiles of lncRNAs and messenger RNAs during NELL-1-induced osteogenesis were obtained using high-throughput sequencing. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene coexpression networks were performed. We identified 323 statistically differentially expressed lncRNAs during osteogenesis and NELL-1-induced osteogenesis, and three lncRNAs (ENST00000602964, ENST00000326734, and TCONS_00006792) were identified as core regulators. Hedgehog pathway markers, including IHH and GLI1, were downregulated, while the antagonists of this pathway (GLI3 and HHIP) were upregulated during NELL-1-induced osteogenesis. In this process, the antagonist of Wnt, SFRP1, was downregulated. According to the analysis, we speculated that lncRNAs played important roles in NELL-1-induced osteogenesis via the crosstalk between Hedgehog and Wnt pathways.

摘要

长链非编码 RNA(lncRNA)是间充质干细胞(MSCs)在细胞分化中重要的调节因子。然而,lncRNA 在 NEL 样 1(NELL-1)诱导的人脂肪来源干细胞成骨分化中的调控机制仍不清楚。通过高通量测序获得 NELL-1 诱导成骨过程中 lncRNA 和信使 RNA 的表达谱。进行基因本体论、京都基因与基因组百科全书通路分析和基因共表达网络分析。我们在成骨过程中和 NELL-1 诱导的成骨过程中鉴定出 323 个统计学上差异表达的 lncRNA,其中三个 lncRNA(ENST00000602964、ENST00000326734 和 TCONS_00006792)被鉴定为核心调节因子。Hedgehog 通路标记物,包括 IHH 和 GLI1,在 NELL-1 诱导的成骨过程中下调,而该通路的拮抗剂(GLI3 和 HHIP)上调。在这个过程中,Wnt 的拮抗剂 SFRP1 下调。根据分析,我们推测 lncRNA 通过 Hedgehog 和 Wnt 通路的串扰在 NELL-1 诱导的成骨中发挥重要作用。

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