数字农科院2.0

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

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

作者机构：

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

期刊名称： Stem Cell Research and Therapy

ISSN： 1757-6512

年卷期： 2022 年 13 卷 1 期

页码：

收录情况： JCR（2021版）

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 ~ 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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