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分离的鼠跟腱固有腱和腱周组织来源祖细胞的转录组谱。

Transcriptome profiles of isolated murine Achilles tendon proper- and peritenon-derived progenitor cells.

机构信息

Department of Animal Science, University of California Davis, 2251 Meyer Hall, One Shields Ave, Davis, California, 95616.

Department of Animal Biosciences, University of Guelph, Ontario, Canada.

出版信息

J Orthop Res. 2019 Jun;37(6):1409-1418. doi: 10.1002/jor.24076. Epub 2018 Jul 13.

Abstract

Progenitor cells of the tendon proper and peritenon have unique properties that could impact their utilization in tendon repair strategies. While a few markers have been found to aid in distinguishing progenitors cells from each region, there is great value in identifying more markers. In this study, we hypothesized that RNAseq could be used to improve our understanding of those markers that define these cell types. Transcriptome profiles were generated for pools of mouse Achilles tendon progenitor cells from both regions and catalogues of potential markers were generated. Moreover, common (e.g., glycoprotein, signaling, and proteinaceous extracellular matrix) and unique (e.g., cartilage development versus angiogenesis and muscle contraction) biological processes and molecular functions were described for progenitors from each region. Real-time quantitative PCR of a subset of genes was used to gain insight into the heterogeneity amongst individual progenitor colonies from each region. Markers like Scx, Mkx, Thbs4, and Wnt10a were consistently able to distinguish tendon proper progenitors from peritenon progenitors; expression variability for other genes suggested greater cell type complexity for potential peritenon progenitor markers. This is the first effort to define Achilles tendon progenitor markers by region. Further efforts to investigate the value of these cataloged markers are required by screening more individual colonies of progenitors for more markers. Clinical Significance: Findings from this study advance efforts in the discernment of cell type specific markers for tendon proper and peritenon progenitor cells; insight into marker sets could improve tracking and sorting strategies for these cells for future therapeutic strategies. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1409-1418, 2019.

摘要

肌腱固有和腱旁组织的祖细胞具有独特的特性,这可能会影响它们在肌腱修复策略中的应用。虽然已经发现了一些标记物来帮助区分来自不同区域的祖细胞,但确定更多的标记物仍然具有重要意义。在这项研究中,我们假设 RNAseq 可用于加深我们对定义这些细胞类型的标记物的理解。为来自两个区域的小鼠跟腱祖细胞池生成了转录组图谱,并生成了潜在标记物的目录。此外,描述了来自每个区域的祖细胞的常见(例如糖蛋白、信号和蛋白质细胞外基质)和独特(例如软骨发育与血管生成和肌肉收缩)的生物学过程和分子功能。对来自每个区域的祖细胞的一组基因进行实时定量 PCR,以深入了解来自每个区域的单个祖细胞集落之间的异质性。Scx、Mkx、Thbs4 和 Wnt10a 等标记物能够一致地区分肌腱固有祖细胞和腱旁祖细胞;其他基因的表达变异性表明潜在的腱旁祖细胞标记物具有更高的细胞类型复杂性。这是首次按区域定义跟腱祖细胞标记物的努力。需要通过筛选更多的祖细胞单个集落来寻找更多的标记物,进一步研究这些标记物的价值。临床意义:这项研究的结果推进了区分肌腱固有和腱旁祖细胞的细胞类型特异性标记物的努力;对标记物集的深入了解可以改善这些细胞的跟踪和分选策略,为未来的治疗策略提供帮助。

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