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

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机构: [1]Translational Medicine Collaborative Innovation Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University,The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen‑ Guangdong 518020, China. [2]Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, Shenzhen 518020, Guangdong, China. [3]Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, Guangdong, China. [4]Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, Guangdong, China. [5]Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China. [6]Kunpeng Institute of Modern Agriculture at Foshan, Foshan 528200, China.
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关键词: Mesenchymal stem cells Osteogenesis Adipogenesis Circular RNAs CRLF1

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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出版当年[2021]版:
大类 | 2 区 医学
小类 | 2 区 细胞与组织工程 2 区 细胞生物学 2 区 医学:研究与实验
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 细胞与组织工程 2 区 细胞生物学 2 区 医学:研究与实验
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出版当年[2020]版:
Q1 CELL & TISSUE ENGINEERING Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q1 CELL & TISSUE ENGINEERING Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Translational Medicine Collaborative Innovation Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University,The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen‑ Guangdong 518020, China. [2]Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, Shenzhen 518020, Guangdong, China. [3]Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, Guangdong, China. [5]Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China.
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通讯机构: [1]Translational Medicine Collaborative Innovation Center, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University,The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen‑ Guangdong 518020, China. [2]Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, Shenzhen 518020, Guangdong, China. [3]Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, Guangdong, China. [4]Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, Guangdong, China.
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