The long non-coding RNA ROCR contributes to SOX9 expression and chondrogenic differentiation of human mesenchymal stem cells.
The long non-coding RNA ROCR contributes to SOX9 expression and chondrogenic differentiation of human mesenchymal stem cells.
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DOI：
10.1242/dev.152504
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Young DA
中科院分区：
文献类型：
--
作者：
Barter MJ;Gomez R;Hyatt S;Cheung K;Skelton AJ;Xu Y;Clark IM;Young DA
长链非编码RNA（lncRNA）以高度组织特异性的方式表达，并在细胞生物学的各个方面发挥作用，通常作为基因表达的关键调控因子。在这项研究中，我们确定了lncRNA在软骨细胞分化中的作用。使用RNA测序，我们从股骨颈骨折患者捐赠的正常髋关节软骨中鉴定了人类关节软骨细胞的lncRNA库。特别感兴趣的是主软骨细胞转录因子SOX 9基因座上游的lncRNA。SOX 9是一种HMG盒转录因子，通过指导软骨细胞特异性基因的表达在软骨细胞发育中发挥重要作用。这些lncRNA中的两种在间充质干细胞（MSC）的软骨形成分化期间上调。这些lncRNA之一，LOC102723505，我们称之为ROCR（软骨形成RNA的调节因子），通过RNA干扰的消耗破坏了MSC软骨形成，伴随着软骨特异性基因表达的减少和基质成分的不完全产生，表明在软骨细胞生物学中的重要作用。具体而言，在不存在ROCR的情况下，S0X9诱导被显著消除，并且S0X9的过表达挽救了MSC向软骨细胞的分化。我们的工作进一步阐明了软骨细胞特异性SOX 9的表达，并强调了一种涉及lncRNA的软骨细胞基因调控的新方法。总结：这项研究鉴定了一种lncRNA的软骨细胞库，并发现ROCR（软骨形成RNA的调节因子）通过促进SOX 9的表达对MSC软骨形成和软骨基因表达很重要。
Long non-coding RNAs (lncRNAs) are expressed in a highly tissue-specific manner and function in various aspects of cell biology, often as key regulators of gene expression. In this study, we established a role for lncRNAs in chondrocyte differentiation. Using RNA sequencing we identified a human articular chondrocyte repertoire of lncRNAs from normal hip cartilage donated by neck of femur fracture patients. Of particular interest are lncRNAs upstream of the master chondrocyte transcription factor SOX9 locus. SOX9 is an HMG-box transcription factor that plays an essential role in chondrocyte development by directing the expression of chondrocyte-specific genes. Two of these lncRNAs are upregulated during chondrogenic differentiation of mesenchymal stem cells (MSCs). Depletion of one of these lncRNAs, LOC102723505, which we termed ROCR (regulator of chondrogenesis RNA), by RNA interference disrupted MSC chondrogenesis, concomitant with reduced cartilage-specific gene expression and incomplete matrix component production, indicating an important role in chondrocyte biology. Specifically, SOX9 induction was significantly ablated in the absence of ROCR, and overexpression of SOX9 rescued the differentiation of MSCs into chondrocytes. Our work sheds further light on chondrocyte-specific SOX9 expression and highlights a novel method of chondrocyte gene regulation involving a lncRNA. Summary: This study identified a chondrocyte repertoire of lncRNAs and discovered that ROCR (regulator of chondrogenesis RNA) is important for MSC chondrogenesis and cartilage gene expression by promoting the expression of SOX9.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
64.8
作者：
Carrieri, Claudia;Cimatti, Laura;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
2.9
作者：
Lefebvre V;Dvir-Ginzberg M
通讯作者：
Dvir-Ginzberg M
影响因子：
14.9
作者：
Flicek P;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt S;Johnson N;Juettemann T;Kähäri AK;Keenan S;Kulesha E;Martin FJ;Maurel T;McLaren WM;Murphy DN;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ruffier M;Sheppard D;Taylor K;Thormann A;Trevanion SJ;Vullo A;Wilder SP;Wilson M;Zadissa A;Aken BL;Birney E;Cunningham F;Harrow J;Herrero J;Hubbard TJ;Kinsella R;Muffato M;Parker A;Spudich G;Yates A;Zerbino DR;Searle SM
通讯作者：
Searle SM
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B