Integrative analysis reveals a lineage-specific circular RNA landscape for adipo-osteogenesis of human mesenchymal stem cells

文献类型： 外文期刊

第一作者： Huang, Hai-Bo

作者： Huang, Hai-Bo;Luo, Hai-Tao;Wei, Na-Na;Liu, Miao-Ling;He, Fei;Yang, Wei;Yang, Xiao-Fei;Li, Fu-Rong;Huang, Hai-Bo;Luo, Hai-Tao;Wei, Na-Na;Liu, Miao-Ling;He, Fei;Yang, Wei;Yang, Xiao-Fei;Li, Fu-Rong;Huang, Hai-Bo;Luo, Hai-Tao;Wei, Na-Na;Liu, Miao-Ling;He, Fei;Yang, Wei;Yang, Xiao-Fei;Li, Fu-Rong;Huang, Hai-Bo;Luo, Hai-Tao;Dong, Jun;Li, Fu-Rong;Dong, Jun;Huang, Hai-Bo;Wei, Na-Na

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关键词： Mesenchymal stem cells; Osteogenesis; Adipogenesis; Circular RNAs; CRLF1

期刊名称：STEM CELL RESEARCH & THERAPY （ 影响因子：8.079； 五年影响因子：8.393 ）

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年卷期： 2022 年 13 卷 1 期

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收录情况： SCI

摘要： Background: The balance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) is critical to skeletal development and diseases. As a research hotspot, circular RNAs (circRNAs) have expanded our understanding of a hidden layer of the transcriptome. Yet, their roles during adipo-osteogenesis remain poorly described. Methods: The identity of human MSCs derived from bone marrow and adipose were first determined by flow cytometry, cellular staining, and quantitative polymerase chain reaction (qPCR). Multi-strategic RNA-sequencing was performed using Poly A, RiboMinus and RiboMinus/RNase R methods. Integrative analysis was performed to identify lineage-specific expressed circRNAs. The structural and expressional characteristics were identified by Sanger sequencing and qPCR, respectively. The regulatory effects of adipogenesis-specific circ-CRLF1 were confirmed using siRNA transcfection and qPCR. Results: We generated a whole transcriptome map during adipo-osteogenesis based on 10 Poly A, 20 RiboMinus and 20 RiboMinus/RNase R datasets. A total of 31,326 circRNAs were identified and quantified from similar to 3.4 billion paired-end reads. Furthermore, the integrative analysis revealed that 1166 circRNA genes exhibited strong lineage-specific expression patterns. Their host genes were enriched in distinct biological functions, such as cell adhesion, cytokine signaling, and cell division. We randomly selected and validated the back-spliced junction sites and expression patterns of 12 lineage-specific circRNAs. Functional analysis indicated that circ-CRLF1 negatively regulated adipogenesis. Conclusions: Our integrative analysis reveals an accurate and generally applicable lineage-specific circRNA landscape for adipo-osteogenesis of MSCs and provides a potential therapeutic target, circ-CRLF1, for the treatment of skeleton-related disease.

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