Whole Transcriptome Analysis of Notochord-Derived Cells during Embryonic Formation of the Nucleus Pulposus.
Whole Transcriptome Analysis of Notochord-Derived Cells during Embryonic Formation of the Nucleus Pulposus.
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DOI：
10.1038/s41598-017-10692-5
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发表时间：
2017-09-05
影响因子：
4.6
通讯作者：
Smith LJ
中科院分区：
文献类型：
--
作者：
Peck SH;McKee KK;Tobias JW;Malhotra NR;Harfe BD;Smith LJ
发育信号的再现代表了治疗椎间盘退变的有前途的策略。在发育过程中，胚胎脊索源性细胞（NDC）是成体髓核（NP）细胞的直接祖细胞，是分泌信号分子的重要来源。本研究的目的是确定全球基因表达谱的NDC在胚胎椎间盘形成的关键阶段。在胚胎第12.5天和出生后第0天从Shh-cre;ROSA：YFP小鼠中分离NDC，代表脊索向NP转化的相对末端。使用RNA-Seq建立了整个发育窗口中总体mRNA丰度的差异。所选分子的蛋白质表达使用免疫组织化学确认。主成分分析显示，聚类的基因表达在每个发育阶段，超过5000个基因显着差异表达E12.5和P0之间。在P0与E12.5时，音刺猬途径元件的mRNA丰度显著较低，而转化生长因子β和胰岛素样生长因子途径元件以及细胞外基质组分（包括胶原蛋白6和聚集蛋白聚糖）的丰度在P0时显著较高。这项研究代表了胚胎NDC的第一个全转录组分析。结果表明，NDC的信号转导和生物合成的变化显着的功能的发育阶段。
Recapitulation of developmental signals represents a promising strategy for treating intervertebral disc degeneration. During development, embryonic notochord-derived cells (NDCs) are the direct progenitors of cells that populate the adult nucleus pulposus (NP) and are an important source of secreted signaling molecules. The objective of this study was to define global gene expression profiles of NDCs at key stages of embryonic disc formation. NDCs were isolated from Shh-cre;ROSA:YFP mice at embryonic day 12.5 and postnatal day 0, representing opposite ends of the notochord to NP transformation. Differences in global mRNA abundance across this developmental window were established using RNA-Seq. Protein expression of selected molecules was confirmed using immunohistochemistry. Principal component analysis revealed clustering of gene expression at each developmental stage with more than 5000 genes significantly differentially expressed between E12.5 and P0. There was significantly lower mRNA abundance of sonic hedgehog pathway elements at P0 vs E12.5, while abundance of elements of the transforming growth factor-beta and insulin-like growth factors pathways, and extracellular matrix components including collagen 6 and aggrecan, were significantly higher at P0. This study represents the first transcriptome-wide analysis of embryonic NDCs. Results suggest signaling and biosynthesis of NDCs change dramatically as a function of developmental stage.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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通讯作者：
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