Transcriptomic analysis identifies novel targets for individual bone morphogenetic protein type 1 receptors in endothelial cells.
Transcriptomic analysis identifies novel targets for individual bone morphogenetic protein type 1 receptors in endothelial cells.
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转录分析识别内皮细胞中单个骨形态发生蛋白1型受体的新靶点。
DOI：
10.1096/fj.202002071r
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Jin SW
中科院分区：
文献类型：
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作者：
Choi W;Lee HW;Pak B;Han O;Kim M;Jin SW
骨形态发生蛋白（BMP）信号调控多种生物过程。在配体结合后，BMP受体（BMPRs）磷酸化SMAD1/5和其他非典型下游效应物，诱导下游靶标的转录。然而，由于下游信号的复杂性和配体-受体相互作用的先天混杂性，单个BMP受体在这一过程中的确切作用在很大程度上仍然未知。为了描述单个bmpr1的独特下游效应，我们分析了表达三种不同组成型活性bmpr1的人脐内皮细胞（HUVECs）的转录组，这些bmpr1在内皮细胞（ECs）中也有表达。从我们的分析中，我们确定了ECs中bmpr1的一些新的下游靶点。更重要的是，我们发现每个BMPR1都有一组独特的下游效应物，这表明每个BMPR1可能在ec中保留独特的功能。综上所述，我们的分析表明，每个BMPR1在内皮细胞中非冗余地调节下游靶点，以产生BMP信号的上下文相关结果。
Bone Morphogenetic Protein (BMP) signaling regulates diverse biological processes. Upon ligand binding, BMP receptors (BMPRs) phosphorylate SMAD1/5 and other non-canonical downstream effectors to induce transcription of downstream targets. However, the precise role of individual BMP receptors in this process remains largely unknown due to the complexity of downstream signaling and the innate promiscuity of ligand-receptor interaction. To delineate unique downstream effectors of individual BMPR1s, we analyzed the transcriptome of human umbilical endothelial cells (HUVECs) expressing three distinct constitutively active BMPR1s of which expression was detected in endothelial cells (ECs). From our analyses, we identified a number of novel downstream targets of BMPR1s in ECs. More importantly, we found that each BMPR1 possesses a distinctive set of downstream effectors, suggesting that each BMPR1 is likely to retain unique function in ECs. Taken together our analyses suggest that each BMPR1 regulates downstream targets non-redundantly in ECs to create context-dependent outcomes of the BMP signaling.